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Special Issue "Alkaloids: Novel Therapeutic Perspectives"

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A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Natural Products".

Deadline for manuscript submissions: closed (31 October 2014)

Special Issue Editors

Guest Editor
Dr. Patrícia Valentão

REQUIMTE/LAQV, Laboratory of Pharmacognosy, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira 228, Porto 4050-313, Portugal
Website | E-Mail
Fax: +351-226093390
Interests: metabolite profiling of natural matrices, marine and terrestrial; evaluation of bioactive agents from natural sources; marine organisms as source of bioactive agents; natural anti-inflammatory agents; neurodegenerative diseases
Guest Editor
Prof. Dr. Mariana Sottomayor

IBMC - Instituto de Biologia Molecular e Celular & Departamento de Biologia, Faculdade de Ciências, Universidade do Porto, Rua de Campo Alegre, 823, 4150-180 Porto, Portugal
E-Mail
Phone: +351220402820

Special Issue Information

Dear Colleagues,

Finding novel bioactive compounds of natural origin has been a major concern for pharmaceuticals research. Among those natural products, alkaloids area among the oldest drugs in medicine and are promising, novel drug candidates.  Alkaloids are characterized by the presence of a basic nitrogen (usually in a heterocycle); they exhibit highly complex structures that are believed to function as herbivorism deterrents in plants. Hence, they show strong physiological activities in animals, which may translate into important therapeutic actions in humans, under adequate dosages. In recent years, the number of new alkaloids isolated, identified, and studied for their medicinal potential has increased. These alkaloids largely originate from unexpected organisms, such as marine sponges, algae, etc. Moreover, the characterization of many novel therapy targets urges the reappraisal of old alkaloids. This Special Issue is devoted to the recent knowledge concerning the potential of alkaloids as therapeutic options for human diseases, their targets, and mechanisms of action.

Prof. Dr. Patricia Valentao
Prof. Dr. Mariana Sottomayor
Guest Editors

Submission

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed Open Access monthly journal published by MDPI.

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Keywords

  • Pyridine group: piperine, coniine, trigonelline, arecaidine, guvacine, pilocarpine, cytisine, nicotine, sparteine, pelletierine.
  • Pyrrolidine group: hygrine, cuscohygrine, nicotine.
  • Tropane group: atropine, cocaine, ecgonine, scopolamine, catuabine.
  • Quinoline group: quinine, quinidine, dihydroquinine, dihydroquinidine, strychnine, brucine, veratrine, cevadine.
  • Isoquinoline group: the opium alkaloids (morphine, codeine, thebaine, isopapa-dimethoxy-aniline, papaverine, narcotine, sanguinarine, narceine, hydrastine, berberine).
  • Phenethylamine group: mescaline, ephedrine, dopamine, amphetamine
  • Indole group: tryptamines (DMT, N-methyltryptamine, psilocybin, serotonin), ergolines: the ergot alkaloids (ergine, ergotamine, lysergic acid, etc.), beta-carbolines (harmine, harmaline, yohimbine, reserpine, emetine), rauwolfia alkaloids (reserpine).
  • Purine group: xanthines (caffeine, theobromine, theophylline).
  • Terpenoid group: aconite alkaloids (aconitine).
  • Steroids: solanine, samandaris, i.e., quaternary ammonium compounds (muscarine, choline, neurine).
  • organic chemistry, natural product chemistry, medicinal chemistry, analytical chemistry, etc.

Published Papers (44 papers)

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Research

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Open AccessArticle Understanding the Physicochemical Properties of Mitragynine, a Principal Alkaloid of Mitragyna speciosa, for Preclinical Evaluation
Molecules 2015, 20(3), 4915-4927; doi:10.3390/molecules20034915
Received: 12 January 2015 / Accepted: 27 February 2015 / Published: 18 March 2015
Cited by 2 | PDF Full-text (720 KB) | HTML Full-text | XML Full-text
Abstract
Varied pharmacological responses have been reported for mitragynine in the literature, but no supportive scientific explanations have been given for this. These studies have been undertaken without a sufficient understanding of the physicochemical properties of mitragynine. In this work a UV spectrophotometer approach
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Varied pharmacological responses have been reported for mitragynine in the literature, but no supportive scientific explanations have been given for this. These studies have been undertaken without a sufficient understanding of the physicochemical properties of mitragynine. In this work a UV spectrophotometer approach and HPLC-UV method were employed to ascertain the physicochemical properties of mitragynine. The pKa of mitragynine measured by conventional UV (8.11 ± 0.11) was in agreement with the microplate reader determination (8.08 ± 0.04). Mitragynine is a lipophilic alkaloid, as indicated by a logP value of 1.73. Mitragynine had poor solubility in water and basic media, and conversely in acidic environments, but it is acid labile. In an in vitro dissolution the total drug release was higher for the simulated gastric fluid but was prolonged and incomplete for the simulated intestinal fluid. The hydrophobicity, poor water solubility, high variability of drug release in simulated biological fluids and acid degradable characteristics of mitragynine probably explain the large variability of its pharmacological responses reported in the literature. The determined physicochemical properties of mitragynine will provide a basis for developing a suitable formulation to further improve its solubility, stability and oral absorption for better assessment of this compound in preclinical studies. Full article
(This article belongs to the Special Issue Alkaloids: Novel Therapeutic Perspectives)
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Open AccessArticle Scopoletin Protects against Methylglyoxal-Induced Hyperglycemia and Insulin Resistance Mediated by Suppression of Advanced Glycation Endproducts (AGEs) Generation and Anti-Glycation
Molecules 2015, 20(2), 2786-2801; doi:10.3390/molecules20022786
Received: 28 October 2014 / Accepted: 3 February 2015 / Published: 9 February 2015
Cited by 5 | PDF Full-text (3574 KB) | HTML Full-text | XML Full-text
Abstract
Recently, several types of foods and drinks, including coffee, cream, and cake, have been found to result in high methylglyoxal (MG) levels in the plasma, thus causing both nutritional and health concerns. MG can be metabolized by phase-II enzymes in liver through the
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Recently, several types of foods and drinks, including coffee, cream, and cake, have been found to result in high methylglyoxal (MG) levels in the plasma, thus causing both nutritional and health concerns. MG can be metabolized by phase-II enzymes in liver through the positive regulation of nuclear factor-erythroid 2-related factor 2 (Nrf2). In this study, we investigated the ability of scopoletin (SP) to protect against MG-induced hyperglycemia and insulin resistance. Recently, SP was shown to be a peroxisome proliferator-activated receptor-γ activator to elevate insulin sensitivity. We investigated the effects of oral administration of SP on the metabolic, biochemical, and molecular abnormalities characteristic of type 2 diabetes in MG-treated Wistar rats to understand the potential mechanism of scopoletin for diabetes protection. Our results suggested that SP activated Nrf2 by Ser40 phosphorylation, resulting in the metabolism of MG into d-lactic acid and the inhibition of AGEs generation, which reduced the accumulation of AGEs in the livers of MG-induced rats. In this manner, SP improved the results of the oral glucose tolerance test and dyslipidemia. Moreover, SP also increased the plasma translocation of glucose transporter-2 and promoted Akt phosphorylation caused by insulin treatment in MG-treated FL83B hepatocytes. In contrast, SP effectively suppressed protein tyrosine phosphatase 1B (PTP1B) expression, thereby alleviating insulin resistance. These findings suggest that SP acts as an anti-glycation and anti-diabetic agent, and thus has therapeutic potential for the prevention of diabetes. Full article
(This article belongs to the Special Issue Alkaloids: Novel Therapeutic Perspectives)
Open AccessArticle Structure-Based Virtual Screening of Novel Natural Alkaloid Derivatives as Potential Binders of h-telo and c-myc DNA G-Quadruplex Conformations
Molecules 2015, 20(1), 206-223; doi:10.3390/molecules20010206
Received: 7 November 2014 / Accepted: 15 December 2014 / Published: 24 December 2014
Cited by 4 | PDF Full-text (2183 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Several ligands can bind to the non-canonical G-quadruplex DNA structures thereby stabilizing them. These molecules can act as effective anticancer agents by stabilizing the telomeric regions of DNA or by regulating oncogene expression. In order to better interact with the quartets of G-quadruplex
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Several ligands can bind to the non-canonical G-quadruplex DNA structures thereby stabilizing them. These molecules can act as effective anticancer agents by stabilizing the telomeric regions of DNA or by regulating oncogene expression. In order to better interact with the quartets of G-quadruplex structures, G-binders are generally characterized by a large aromatic core involved in π-π stacking. Some natural flexible cyclic molecules from Traditional Chinese Medicine have shown high binding affinity with G-quadruplex, such as berbamine and many other alkaloids. Using the structural information available on G-quadruplex structures, we performed a high throughput in silico screening of commercially available alkaloid derivative databases by means of a structure-based approach based on docking and molecular dynamics simulations against the human telomeric sequence d[AG3(T2AG3)3] and the c-myc promoter structure. We identified 69 best hits reporting an improved theoretical binding affinity with respect to the active set. Among them, a berberine derivative, already known to remarkably inhibit telomerase activity, was related to a better theoretical affinity versus c-myc. Full article
(This article belongs to the Special Issue Alkaloids: Novel Therapeutic Perspectives)
Open AccessArticle Toxicity of Evodiae fructus on Rat Liver Mitochondria: The Role of Oxidative Stress and Mitochondrial Permeability Transition
Molecules 2014, 19(12), 21168-21182; doi:10.3390/molecules191221168
Received: 30 September 2014 / Revised: 2 December 2014 / Accepted: 11 December 2014 / Published: 16 December 2014
Cited by 6 | PDF Full-text (1801 KB) | HTML Full-text | XML Full-text
Abstract
Evodiae fructus (EF) has been used in China for thousands of years as an analgesic, antiemetic, anti-inflammatory and antidiarrheal drug. EF is a toxic drug and causes hepatotoxicity in humans. Although recent chronic toxicity studies performed on aqueous extract of EF has revealed
[...] Read more.
Evodiae fructus (EF) has been used in China for thousands of years as an analgesic, antiemetic, anti-inflammatory and antidiarrheal drug. EF is a toxic drug and causes hepatotoxicity in humans. Although recent chronic toxicity studies performed on aqueous extract of EF has revealed that it can produce obvious cumulative hepatotoxicity, the mechanism behind this toxicity is still uncertain. In the present study, we investigated the influence of EF on oxidative stress, mitochondrial permeability transition, adenosine triphosphate (ATP), and cytochrome C release of hepatic mitochondria. Rats were divided into four groups and fed distilled water, 6, 12, 24 g/kg of aqueous extract of EF daily for 15 days. Evodiamine, rutaecarpine and evodine were quantified in the aqueous extract by high performance liquid chromatography with ultraviolet detection (HPLC/UV). The results showed that aqueous extract of EF could significantly (p < 0.05) decrease MnSOD levels to 56.50%, 46.77% and 19.67% of control group, GSH level was decreased to 74.24%, 53.97% and 47.91% of control group and MDA level was increased to 131.55%, 134.34% and 150.81% of control group in the 6, 12 and 24 g/kg groups, respectively; extract also induced mitochondria swelling, vacuolation, MPT pore opening and a significant decrease (p < 0.05) in mitochondrial potential, while ATP levels were significant decreased (p < 0.05) to 65.24%, 38.08% and 34.59% of control group in the 6, 12 and 24 g/kg groups, respectively, resulting in ATP depletion and CytC release, finally trigger cell death signaling, which are the partial hepatotoxicity mechanisms of EF. Full article
(This article belongs to the Special Issue Alkaloids: Novel Therapeutic Perspectives)
Open AccessArticle Antioxidant and Anticancer Aporphine Alkaloids from the Leaves of Nelumbo nucifera Gaertn. cv. Rosa-plena
Molecules 2014, 19(11), 17829-17838; doi:10.3390/molecules191117829
Received: 2 September 2014 / Revised: 28 October 2014 / Accepted: 31 October 2014 / Published: 3 November 2014
Cited by 12 | PDF Full-text (267 KB) | HTML Full-text | XML Full-text
Abstract
Fifteen compounds were extracted and purified from the leaves of Nelumbo nucifera Gaertn. cv. Rosa-plena. These compounds include liriodenine (1), lysicamine (2), (−)-anonaine (3), (−)-asimilobine (4), (−)-caaverine (5), (−)-N-methylasimilobine (
[...] Read more.
Fifteen compounds were extracted and purified from the leaves of Nelumbo nucifera Gaertn. cv. Rosa-plena. These compounds include liriodenine (1), lysicamine (2), (−)-anonaine (3), (−)-asimilobine (4), (−)-caaverine (5), (−)-N-methylasimilobine (6), (−)-nuciferine (7), (−)-nornuciferine (8), (−)-roemerine (9), 7-hydroxydehydronuciferine (10) cepharadione B (11), β-sitostenone (12), stigmasta-4,22-dien-3-one (13) and two chlorophylls: pheophytin-a (14) and aristophyll-C (15). The anti-oxidation activity of the compounds was examined by antiradical scavenging, metal chelating and ferric reducing power assays. The results have shown that these compounds have antioxidative activity. The study has also examined the antiproliferation activity of the isolated compounds against human melanoma, prostate and gastric cancer cells. The results shown that 7-hydroxydehydronuciferine (10) significantly inhibited the proliferation of melanoma, prostate and gastric cancer cells. Together, these findings suggest that leaves of Nelumbo nucifera Gaertn. cv. Rosa-plena are a good resource for obtaining the biologically active substances with antioxidant properties. Full article
(This article belongs to the Special Issue Alkaloids: Novel Therapeutic Perspectives)
Open AccessArticle Assessment of Mechanisms Involved in Antinociception Produced by the Alkaloid Caulerpine
Molecules 2014, 19(9), 14699-14709; doi:10.3390/molecules190914699
Received: 15 August 2014 / Revised: 7 September 2014 / Accepted: 9 September 2014 / Published: 16 September 2014
Cited by 4 | PDF Full-text (852 KB) | HTML Full-text | XML Full-text
Abstract
In previous works we showed that oral administration of caulerpine, a bisindole alkaloid isolated from algae of the genus Caulerpa, produced antinociception when assessed in chemical and thermal models of nociception. In this study, we evaluated the possible mechanism of action of
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In previous works we showed that oral administration of caulerpine, a bisindole alkaloid isolated from algae of the genus Caulerpa, produced antinociception when assessed in chemical and thermal models of nociception. In this study, we evaluated the possible mechanism of action of this alkaloid in mice, using the writhing test. The antinociceptive effect of caulerpine was not affected by intraperitoneal (i.p.) pretreatment of mice with naloxone, flumazenil, l-arginine or atropine, thus discounting the involvement of the opioid, GABAergic, l-arginine-nitric oxide and (muscarinic) cholinergic pathways, respectively. In contrast, i.p. pretreatment with yohimbine, an α2-adrenoceptor antagonist, or tropisetron, a 5-HT3 antagonist, significantly blocked caulerpine-induced antinociception. These results suggest that caulerpine exerts its antinociceptive effect in the writhing test via pathways involving α2-adrenoceptors and 5-HT3 receptors. In summary, this alkaloid could be of interest in the development of new dual-action analgesic drugs. Full article
(This article belongs to the Special Issue Alkaloids: Novel Therapeutic Perspectives)
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Open AccessArticle Preparative Isolation of Seven Diterpenoid Alkaloids from Aconitum coreanum by pH-Zone-Refining Counter-Current Chromatography
Molecules 2014, 19(8), 12619-12629; doi:10.3390/molecules190812619
Received: 1 August 2014 / Revised: 9 August 2014 / Accepted: 11 August 2014 / Published: 19 August 2014
Cited by 5 | PDF Full-text (985 KB) | HTML Full-text | XML Full-text
Abstract
The aim of this paper was to seek an efficient method to preparative separation of alkaloid compounds from Aconitum coreanum (Guanbaifu), a well-known traditional Chinese medicinal plant for heart disease. Seven alkaloid compounds were successfully purified by pH-zone-refining counter-current chromatography with two-phase solvent
[...] Read more.
The aim of this paper was to seek an efficient method to preparative separation of alkaloid compounds from Aconitum coreanum (Guanbaifu), a well-known traditional Chinese medicinal plant for heart disease. Seven alkaloid compounds were successfully purified by pH-zone-refining counter-current chromatography with two-phase solvent system of petroleum ether–ethyl acetate–methanol–water (5:5:1:9, v/v/v/v), 10 mM triethylamine in upper phase and 10 mM hydrochloric acid in lower phase. From 3.5 g of crude extract, 356 mg of Guanfu base I, 578 mg of Guanfu base A, 74 mg of atisine, 94 mg of Guanfu base F, 423 mg of Guanfu base G, 67 mg of Guanfu base R and 154 mg of Guanfu base P were obtained with the purity of 96.40%, 97.2%, 97.5%, 98.1%, 98.9%, 98.3% and 98.4%. Their chemical structures were identified by TOF-MS and 1H-NMR. This study indicated that pH-zone-refining counter-current chromatography was an efficient method for separating the kind of alkaloids with low absorbance values. Full article
(This article belongs to the Special Issue Alkaloids: Novel Therapeutic Perspectives)
Open AccessArticle α-Solanine Inhibits Invasion of Human Prostate Cancer Cell by Suppressing Epithelial-Mesenchymal Transition and MMPs Expression
Molecules 2014, 19(8), 11896-11914; doi:10.3390/molecules190811896
Received: 25 June 2014 / Revised: 2 August 2014 / Accepted: 5 August 2014 / Published: 11 August 2014
Cited by 12 | PDF Full-text (2158 KB) | HTML Full-text | XML Full-text
Abstract
α-Solanine, a naturally occurring steroidal glycoalkaloid found in nightshade (Solanum nigrum Linn.), was found to inhibit proliferation and induce apoptosis of tumor cells. However, the mechanism involved in suppression of cancer cell metastasis by α-solanine remains unclear. This study investigates the suppression mechanism
[...] Read more.
α-Solanine, a naturally occurring steroidal glycoalkaloid found in nightshade (Solanum nigrum Linn.), was found to inhibit proliferation and induce apoptosis of tumor cells. However, the mechanism involved in suppression of cancer cell metastasis by α-solanine remains unclear. This study investigates the suppression mechanism of α-solanine on motility of the human prostate cancer cell PC-3. Results show that α-solanine reduces the viability of PC-3 cells. When treated with non-toxic doses of α-solanine, cell invasion is markedly suppressed by α-solanine. α-Solanine also significantly elevates epithelial marker E-cadherin expression, while it concomitantly decreases mesenchymal marker vimentin expression, suggesting it suppresses epithelial-mesenchymal transition (EMT). α-Solanine reduces the mRNA level of matrix metalloproteinase-2 (MMP-2), MMP-9 and extracellular inducer of matrix metalloproteinase (EMMPRIN), but increases the expression of reversion-inducing cysteine-rich protein with kazal motifs (RECK), and tissue inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2. Immunoblotting assays indicate α-solanine is effective in suppressing the phosphorylation of phosphatidylinositide-3 kinase (PI3K), Akt and ERK. Moreover, α-solanine downregulates oncogenic microRNA-21 (miR-21) and upregulates tumor suppressor miR-138 expression. Taken together, the results suggest that inhibition of PC-3 cell invasion by α-solanine may be, at least in part, through blocking EMT and MMPs expression. α-Solanine also reduces ERK and PI3K/Akt signaling pathways and regulates expression of miR-21 and miR-138. These findings suggest an attractive therapeutic potential of α-solanine for suppressing invasion of prostate cancer cell. Full article
(This article belongs to the Special Issue Alkaloids: Novel Therapeutic Perspectives)
Open AccessArticle Lycodine-Type Alkaloids from Lycopodiastrum casuarinoides and Their Acetylcholinesterase Inhibitory Activity
Molecules 2014, 19(7), 9999-10010; doi:10.3390/molecules19079999
Received: 23 May 2014 / Revised: 18 June 2014 / Accepted: 27 June 2014 / Published: 10 July 2014
Cited by 6 | PDF Full-text (379 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Four new lycodine-type alkaloids, namely 16-hydroxyhuperzine B (1), N-methyl-11-acetoxyhuperzine B (2), 8,15-dihydrolycoparin A (3) and (7S,12S,13R)-huperzine D-16-O-β-d-glucopyranoside (4), along with ten known analogues 514
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Four new lycodine-type alkaloids, namely 16-hydroxyhuperzine B (1), N-methyl-11-acetoxyhuperzine B (2), 8,15-dihydrolycoparin A (3) and (7S,12S,13R)-huperzine D-16-O-β-d-glucopyranoside (4), along with ten known analogues 514, were isolated from the whole plant of Lycopodiastrum casuarinoides. The structures of the new compounds were elucidated by means of spectroscopic techniques (IR, MS, NMR, and CD) and chemical methods. Compounds 1 and 2 possessed four connected six-membered rings, while compounds 3 and 4 were piperidine ring cleavage products. In particular, compound 4 was a lycopodium alkaloidal glycoside which is reported for the first time. Among the isolated compounds N-demethylhuperzinine (7), huperzine C (8), huperzine B (9) and lycoparin C (13) possessed significant inhibitory activity against acetylcholinesterase, and the new compound 1 showed moderate inhibitory activity. The structure activity relationships were discussed. Full article
(This article belongs to the Special Issue Alkaloids: Novel Therapeutic Perspectives)
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Open AccessArticle Cytotoxic Aporphine Alkaloids from Leaves and Twigs of Pseuduvaria trimera (Craib)
Molecules 2014, 19(7), 8762-8772; doi:10.3390/molecules19078762
Received: 21 May 2014 / Revised: 17 June 2014 / Accepted: 19 June 2014 / Published: 25 June 2014
PDF Full-text (334 KB) | HTML Full-text | XML Full-text
Abstract
From ethyl acetate-methanol extracts of leaves and twigs of Pseuduvaria trimera a new aporphine alkaloid; 8-hydroxy-1,4,5-trimethoxy-7-oxoaporphine or 8-hydroxyartabonatine C (1) was isolated, together with the known 1,2,3-trimethoxy-4,5-dioxo-6a,7-dehydroaporphine (ouregidione, 2). Their structures were elucidated by a combination of spectral methods; mainly
[...] Read more.
From ethyl acetate-methanol extracts of leaves and twigs of Pseuduvaria trimera a new aporphine alkaloid; 8-hydroxy-1,4,5-trimethoxy-7-oxoaporphine or 8-hydroxyartabonatine C (1) was isolated, together with the known 1,2,3-trimethoxy-4,5-dioxo-6a,7-dehydroaporphine (ouregidione, 2). Their structures were elucidated by a combination of spectral methods; mainly 2D NMR; IR and MS. Compounds 1 and 2 exhibited cytotoxic activity with IC50 values of 26.36 ± 5.18 μM and 12.88 ± 2.49 μM, respectively, for human hepatocellular carcinoma HepG2 cells, and 64.75 ± 4.45 and 67.06 ± 3.5 μM, respectively, for human breast cancer MDA-MB231 cells. Both compounds displayed anti-cancer activity but less than that of doxorubicin; a conventional chemotherapeutic drug, the IC50 levels of which were 2.21 ± 1.72 and 1.83 ± 0.09 μM for HepG2 and MDA-MB231 cells, respectively. Full article
(This article belongs to the Special Issue Alkaloids: Novel Therapeutic Perspectives)
Open AccessArticle Acetylcholinesterase-inhibiting Alkaloids from Zephyranthes concolor
Molecules 2011, 16(11), 9520-9533; doi:10.3390/molecules16119520
Received: 17 October 2011 / Revised: 27 October 2011 / Accepted: 7 November 2011 / Published: 15 November 2011
Cited by 14 | PDF Full-text (250 KB) | Supplementary Files
Abstract
The bulbs and aerial parts of Zephyranthes concolor (Lindl.) Benth. & Hook. f. (Amaryllidaceae), an endemic species to Mexico, were found to contain the alkaloids chlidanthine, galanthamine, galanthamine N-oxide, lycorine, galwesine, and epinorgalanthamine. Since currently only partial and low resolution 1H-NMR data
[...] Read more.
The bulbs and aerial parts of Zephyranthes concolor (Lindl.) Benth. & Hook. f. (Amaryllidaceae), an endemic species to Mexico, were found to contain the alkaloids chlidanthine, galanthamine, galanthamine N-oxide, lycorine, galwesine, and epinorgalanthamine. Since currently only partial and low resolution 1H-NMR data for chlidanthine acetate are available, and none for chlidanthine, its 1D and 2D high resolution 1H- and 13C-NMR spectra were recorded. Unambiguous assignations were achieved with HMBC, and HSQC experiments, and its structure was corroborated by X-ray diffraction. Minimum energy conformation for structures of chlidanthine, and its positional isomer galanthamine, were calculated by molecular modelling. Galanthamine is a well known acetylcholinesterase inhibitor; therefore, the isolated alkaloids were tested for this activity. Chlidanthine and galanthamine N-oxide inhibited electric eel acetylcholinesterase (2.4 and 2.6 × 10−5 M, respectively), indicating they are about five times less potent than galanthamine, while galwesine was inactive at 10−3 M. Inhibitory activity of HIV-1 replication, and cytotoxicity of the isolated alkaloids were evaluated in human MT-4 cells; however, the alkaloids showed poor activity as compared with standard anti-HIV drugs, but most of them were not cytotoxic. Full article
(This article belongs to the Special Issue Alkaloids: Novel Therapeutic Perspectives)
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Open AccessArticle Polar Compounds Isolated from the Leaves of Albertisia delagoensis (Menispermaceae)
Molecules 2011, 16(11), 9153-9160; doi:10.3390/molecules16119153
Received: 8 October 2011 / Revised: 21 October 2011 / Accepted: 27 October 2011 / Published: 2 November 2011
PDF Full-text (193 KB)
Abstract
Aqueous infusions of the leaves of the shrub Albertisia delagoensis (Menispermaceae) are used in South Africa in traditional Zulu medicine to alleviate a variety of symptoms, including fever, and intestinal problems. We report the analysis of such an aqueous extract using the HPLC-NMR
[...] Read more.
Aqueous infusions of the leaves of the shrub Albertisia delagoensis (Menispermaceae) are used in South Africa in traditional Zulu medicine to alleviate a variety of symptoms, including fever, and intestinal problems. We report the analysis of such an aqueous extract using the HPLC-NMR technique. A number of polar compounds were identified, including proto-quercitol, nicotinic acid, allantoic acid, 3,4-dihydroxy-benzoic acid, phthalic acid and the aporphine alkaloid derivative roemrefidine. Allantoic acid and roemrefidine have been fully characterised by 1H- and 13C-NMR and mass spectrometry. Earlier reports of antiplasmodial activity of roemrefidine and of A. delagoensis extracts are correlated with this study and with the antipyretic properties of neutral aqueous extracts. Full article
(This article belongs to the Special Issue Alkaloids: Novel Therapeutic Perspectives)
Open AccessArticle Application of Preparative High-Speed Counter-Current Chromatography for the Separation of Two Alkaloids from the Roots of Tabernaemontana catharinensis (Apocynaceae)
Molecules 2011, 16(9), 7480-7487; doi:10.3390/molecules16097480
Received: 28 June 2011 / Revised: 16 August 2011 / Accepted: 31 August 2011 / Published: 2 September 2011
Cited by 5 | PDF Full-text (544 KB)
Abstract
The methanolic extract of Tabernaemontana catharinensis (Apocynaceae) roots, which contains alkaloids with several biological activities, was separated on a preparative scale using high-speed counter-current chromatography. The optimum solvent system was found to be a mixture of CHCl3-MeOH-H2O [5:10:6 (
[...] Read more.
The methanolic extract of Tabernaemontana catharinensis (Apocynaceae) roots, which contains alkaloids with several biological activities, was separated on a preparative scale using high-speed counter-current chromatography. The optimum solvent system was found to be a mixture of CHCl3-MeOH-H2O [5:10:6 (v/v/v)] and led to a successful separation of two monoterpenic indole alkaloids, voachalotine (1) and 12-methoxy-Nb-methylvoachalotine (2) in approximately 4.0 hours. The alkaloids were all isolated at purities over 95%, and their structures were established on the basis of spectroscopic methods, including 1D and 2D NMR and EI/MS. Full article
(This article belongs to the Special Issue Alkaloids: Novel Therapeutic Perspectives)
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Open AccessArticle Evaluation of the Effects of Mitragyna speciosa Alkaloid Extract on Cytochrome P450 Enzymes Using a High Throughput Assay
Molecules 2011, 16(9), 7344-7356; doi:10.3390/molecules16097344
Received: 4 July 2011 / Revised: 8 August 2011 / Accepted: 19 August 2011 / Published: 29 August 2011
Cited by 22 | PDF Full-text (492 KB)
Abstract
The extract from Mitragyna speciosa has been widely used as an opium substitute, mainly due to its morphine-like pharmacological effects. This study investigated the effects of M. speciosa alkaloid extract (MSE) on human recombinant cytochrome P450 (CYP) enzyme activities using a modified Crespi
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The extract from Mitragyna speciosa has been widely used as an opium substitute, mainly due to its morphine-like pharmacological effects. This study investigated the effects of M. speciosa alkaloid extract (MSE) on human recombinant cytochrome P450 (CYP) enzyme activities using a modified Crespi method. As compared with the liquid chromatography-mass spectrometry method, this method has shown to be a fast and cost-effective way to perform CYP inhibition studies. The results indicated that MSE has the most potent inhibitory effect on CYP3A4 and CYP2D6, with apparent half-maximal inhibitory concentration (IC50) values of 0.78 µg/mL and 0.636 µg/mL, respectively. In addition, moderate inhibition was observed for CYP1A2, with an IC50 of 39 µg/mL, and weak inhibition was detected for CYP2C19. The IC50 of CYP2C19 could not be determined, however, because inhibition was < 50%. Competitive inhibition was found for the MSE-treated CYP2D6 inhibition assay, whereas non-competitive inhibition was shown in inhibition assays using CYP3A4, CYP1A2 and CYP2C19. Quinidine (CYP2D6), ketoconazole (CYP3A4), tranylcypromine (CYP2C19) and furafylline (CYP1A2) were used as positive controls throughout the experiments. This study shows that MSE may contribute to an herb-drug interaction if administered concomitantly with drugs that are substrates for CYP3A4, CYP2D6 and CYP1A2. Full article
(This article belongs to the Special Issue Alkaloids: Novel Therapeutic Perspectives)
Open AccessArticle Chirality and Numbering of Substituted Tropane Alkaloids
Molecules 2011, 16(9), 7199-7209; doi:10.3390/molecules16097199
Received: 12 July 2011 / Revised: 16 August 2011 / Accepted: 17 August 2011 / Published: 25 August 2011
Cited by 6 | PDF Full-text (554 KB)
Abstract
The strict application of IUPAC rules for the numbering of tropane alkaloids is not always applied by authors and there is hence a lot of confusion in the literature. In most cases, the notation of 3, 6/7-disubstituted derivatives has been chosen arbitrarily, based
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The strict application of IUPAC rules for the numbering of tropane alkaloids is not always applied by authors and there is hence a lot of confusion in the literature. In most cases, the notation of 3, 6/7-disubstituted derivatives has been chosen arbitrarily, based on NMR and MS data, without taking into account the absolute configuration of these two carbons. This paper discusses the problem and the relevance of CD and NMR to determine molecular configurations. We report on the use of 1H-NMR anisochrony (Δd) induced by the Mosher’s chiral auxiliary reagents (R)-(-)- and (S)-(+)-α-methoxy-α-trifluoromethyl-phenylacetyl chlorides (MTPA-Cl), to determine the absolute configuration of (3R,6R)-3α-hydroxy-6b-senecioyloxytropane, a disubstituted tropane alkaloid isolated from the aerial parts of Schizanthus grahamii (Solanaceae). These analytical tools should help future works in correctly assigning the configuration of additional 3, 6/7 disubstituted tropane derivatives. Full article
(This article belongs to the Special Issue Alkaloids: Novel Therapeutic Perspectives)
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Open AccessArticle The Growth Suppressing Effects of Girinimbine on Hepg2 Involve Induction of Apoptosis and Cell Cycle Arrest
Molecules 2011, 16(8), 7155-7170; doi:10.3390/molecules16087155
Received: 18 May 2011 / Revised: 6 July 2011 / Accepted: 3 August 2011 / Published: 23 August 2011
Cited by 23 | PDF Full-text (2020 KB)
Abstract
Murraya koenigii is an edible herb widely used in folk medicine. Here we report that girinimbine, a carbazole alkaloid isolated from this plant, inhibited the growth and induced apoptosis in human hepatocellular carcinoma, HepG2 cells. The MTT and LDH assay results showed that
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Murraya koenigii is an edible herb widely used in folk medicine. Here we report that girinimbine, a carbazole alkaloid isolated from this plant, inhibited the growth and induced apoptosis in human hepatocellular carcinoma, HepG2 cells. The MTT and LDH assay results showed that girinimbine decreased cell viability and increased cytotoxicity in a dose-and time-dependent manner selectively. Girinimbine-treated HepG2 cells showed typical morphological features of apoptosis, as observed from normal inverted microscopy and Hoechst 33342 assay. Furthermore, girinimbine treatment resulted in DNA fragmentation and elevated levels of caspase-3 in HepG2 cells. Girinimbine treatment also displayed a time-dependent accumulation of the Sub-G0/G1 peak (hypodiploid) and caused G0/G1-phase arrest. Together, these results demonstrated for the first time that girinimbine could effectively induce programmed cell death in HepG2 cells and suggests the importance of conducting further investigations in preclinical human hepatocellular carcinoma models, especially on in vivo efficacy, to promote girinimbine for use as an anticancer agent against hepatocellular carcinoma. Full article
(This article belongs to the Special Issue Alkaloids: Novel Therapeutic Perspectives)
Open AccessCommunication Azaphenanthrene Alkaloids with Antitumoral Activity from Anaxagorea dolichocarpa Sprague & Sandwith (Annonaceae)
Molecules 2011, 16(8), 7125-7131; doi:10.3390/molecules16087125
Received: 27 June 2011 / Revised: 26 July 2011 / Accepted: 4 August 2011 / Published: 22 August 2011
Cited by 7 | PDF Full-text (432 KB)
Abstract
Phytochemical investigation of Anaxagorea dolichocarpa Sprague & Sandwith led to isolation of three azaphenanthrene alkaloids: eupolauramine, sampangine and imbiline 1. Their chemical structures were established on the basis of spectroscopic data from IR, HR-ESI-MS, NMR (including 2D experiments) and comparison with the literature.
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Phytochemical investigation of Anaxagorea dolichocarpa Sprague & Sandwith led to isolation of three azaphenanthrene alkaloids: eupolauramine, sampangine and imbiline 1. Their chemical structures were established on the basis of spectroscopic data from IR, HR-ESI-MS, NMR (including 2D experiments) and comparison with the literature. Sampangine and imbiline 1 are being described in the Anaxagorea genus for the first time. Eupolauramine and sampangine show concentration-dependent antitumoral activity in leukemic cells K562 with IC50 of 18.97 and 10.95 µg/mL, respectively. Full article
(This article belongs to the Special Issue Alkaloids: Novel Therapeutic Perspectives)
Open AccessArticle Alkaloids from Hippeastrum papilio
Molecules 2011, 16(8), 7097-7104; doi:10.3390/molecules16087097
Received: 9 June 2011 / Revised: 20 July 2011 / Accepted: 26 July 2011 / Published: 18 August 2011
Cited by 18 | PDF Full-text (438 KB)
Abstract
Galanthamine, an acetylcholinesterase inhibitor marketed as a hydrobromide salt (Razadyne®, Reminyl®) for the treatment of Alzheimer’s disease (AD), is obtained from Amaryllidaceae plants, especially those belonging to the genera Leucojum, Narcissus, Lycoris and Ungernia. The growing demand for galanthamine has
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Galanthamine, an acetylcholinesterase inhibitor marketed as a hydrobromide salt (Razadyne®, Reminyl®) for the treatment of Alzheimer’s disease (AD), is obtained from Amaryllidaceae plants, especially those belonging to the genera Leucojum, Narcissus, Lycoris and Ungernia. The growing demand for galanthamine has prompted searches for new sources of this compound, as well as other bioactive alkaloids for the treatment of AD. In this paper we report the isolation of the new alkaloid 11β-hydroxygalanthamine, an epimer of the previously isolated alkaloid habranthine, which was identified using NMR techniques. It has been shown that 11β-hydroxygalanthamine has an important in vitro acetylcholinesterase inhibitory activity. Additionally, Hippeastrum papilio yielded substantial quantities of galanthamine. Full article
(This article belongs to the Special Issue Alkaloids: Novel Therapeutic Perspectives)
Open AccessArticle Rauniticine-allo-Oxindole B and Rauniticinic-allo Acid B, New Heteroyohimbine-Type Oxindole Alkaloids from the Stems of Malaysian Uncaria longiflora var. pteropoda
Molecules 2011, 16(8), 6541-6548; doi:10.3390/molecules16086541
Received: 20 June 2011 / Revised: 15 July 2011 / Accepted: 20 July 2011 / Published: 4 August 2011
Cited by 5 | PDF Full-text (374 KB)
Abstract Two new heteroyohimbine-type oxindole alkaloids, rauniticine-allo-oxindole B and rauniticinic-allo acid B, have been successfully isolated from the stems extract of Malaysian Uncaria longiflora var. pteropoda. The structures of the two new alkaloids were determined by spectroscopic analysis. Full article
(This article belongs to the Special Issue Alkaloids: Novel Therapeutic Perspectives)
Open AccessArticle Acute Oral Toxicity of Methanolic Seed Extract of Cassia fistula in Mice
Molecules 2011, 16(6), 5268-5282; doi:10.3390/molecules16065268
Received: 23 May 2011 / Accepted: 22 June 2011 / Published: 23 June 2011
Cited by 26 | PDF Full-text (653 KB)
Abstract
Background and objective: Cassia fistula is widely used in traditional medicine to treat various types of ailments. The evaluation of toxic properties of C. fistula is crucial when considering public health protection because exposure to plant extracts can result in undesirable effects on
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Background and objective: Cassia fistula is widely used in traditional medicine to treat various types of ailments. The evaluation of toxic properties of C. fistula is crucial when considering public health protection because exposure to plant extracts can result in undesirable effects on consumers. Hence, in this study the acute oral toxicity of C. fistula seeds extract was investigated in mice. Results: Oral administration of crude extract at the highest dose of 5000 mg/kg resulted in no mortalities or evidence of adverse effects, implying that C. fistula in nontoxic. Throughout 14 days of the treatment no changes in behavioural pattern, clinical sign and body weight of mice in both control and treatment groups. Also there were no any significant elevations observed in the biochemical analysis of the blood serum. Further, histopathological examination revealed normal architecture and no significant adverse effects observed on the kidney, heart, liver, lung and spleen. Conclusions: Overall, the results suggest that, the oral administration of C. fistula methanolic seeds extract did not produce any significant toxic effect in mice. Hence, the extract can be utilized for pharmaceutical formulations. Full article
(This article belongs to the Special Issue Alkaloids: Novel Therapeutic Perspectives)
Open AccessArticle Identification of Diterpenoid Alkaloids from the Roots of Aconitum kusnezoffii Reihcb.
Molecules 2011, 16(4), 3345-3350; doi:10.3390/molecules16043345
Received: 22 February 2011 / Revised: 26 March 2011 / Accepted: 30 March 2011 / Published: 19 April 2011
Cited by 7 | PDF Full-text (140 KB) | Supplementary Files
Abstract Three diterpenoid alkaloids, including an unreported compound, were isolated from the roots of Aconitum kusnezoffii Reichb. On the basis of spectral analysis, these three compounds were determined to be 1,15-dimethoxy-3-hydroxy-14-benzoyl-16-ketoneoline, benzoylaconine and aconitine. Full article
(This article belongs to the Special Issue Alkaloids: Novel Therapeutic Perspectives)
Open AccessArticle Alkaloids Induce Programmed Cell Death in Bloodstream Forms of Trypanosomes (Trypanosoma b. brucei)
Molecules 2008, 13(10), 2462-2473; doi:10.3390/molecules13102462
Received: 30 June 2008 / Revised: 5 September 2008 / Accepted: 30 September 2008 / Published: 3 October 2008
Cited by 41 | PDF Full-text (203 KB) | HTML Full-text | XML Full-text
Abstract
The potential induction of a programmed cell death (PCD) in Trypanosoma b. brucei by 55 alkaloids of the quinoline, quinolizidine, isoquinoline, indole, terpene, tropane, steroid, and piperidine type was studied by measuring DNA fragmentation and changes in mitochondrial membrane potential. For comparison, the
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The potential induction of a programmed cell death (PCD) in Trypanosoma b. brucei by 55 alkaloids of the quinoline, quinolizidine, isoquinoline, indole, terpene, tropane, steroid, and piperidine type was studied by measuring DNA fragmentation and changes in mitochondrial membrane potential. For comparison, the induction of apoptosis by the same alkaloids in human leukemia cells (Jurkat APO-S) was tested. Several alkaloids of the isoquinoline, quinoline, indole and steroidal type (berberine, chelerythrine, emetine, sanguinarine, quinine, ajmalicine, ergotamine, harmine, vinblastine, vincristine, colchicine, chaconine, demissidine and veratridine) induced programmed cell death, whereas quinolizidine, tropane, terpene and piperidine alkaloids were mostly inactive. Effective PCD induction (EC50 below 10 µM) was caused in T. brucei by chelerythrine, emetine, sanguinarine, and chaconine. The active alkaloids can be characterized by their general property to inhibit protein biosynthesis, to intercalate DNA, to disturb membrane fluidity or to inhibit microtubule formation. Full article
(This article belongs to the Special Issue Alkaloids: Novel Therapeutic Perspectives)
Open AccessArticle A Simple, Rapid and Mild One Pot Synthesis of Benzene Ring Acylated and Demethylated Analogues of Harmine under Solvent-free Conditions
Molecules 2008, 13(8), 1584-1598; doi:10.3390/molecules1301584
Received: 6 May 2008 / Revised: 24 June 2008 / Accepted: 23 July 2008 / Published: 6 August 2008
Cited by 2 | PDF Full-text (221 KB) | HTML Full-text | XML Full-text
Abstract
A simple, rapid, solvent-free, room temperature one pot synthesis of benzene ring acylated and demethylated analogues of harmine using acyl halides/acid anhydrides and AlCl3 has been developed. Eight different acyl halides/acid anhydrides were used in the synthesis. The resulting mixture of products
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A simple, rapid, solvent-free, room temperature one pot synthesis of benzene ring acylated and demethylated analogues of harmine using acyl halides/acid anhydrides and AlCl3 has been developed. Eight different acyl halides/acid anhydrides were used in the synthesis. The resulting mixture of products was separated by column chromatography to afford 10- and 12-monoacyl analogues, along with 10,12-diacyl-11-hydroxy products. In five cases the corresponding 10-acyl-11-hydroxy analogues were also obtained. Yields from the eight syntheses (29 products in total) were in the 6-34% range and all compounds were fully characterized. Full article
(This article belongs to the Special Issue Alkaloids: Novel Therapeutic Perspectives)
Open AccessArticle HPLC-ESI-MS/MS of Imidazole Alkaloids in Pilocarpus microphyllus
Molecules 2008, 13(7), 1518-1529; doi:10.3390/molecules13071518
Received: 28 May 2008 / Revised: 22 June 2008 / Accepted: 18 July 2008 / Published: 30 July 2008
Cited by 13 | PDF Full-text (323 KB) | HTML Full-text | XML Full-text
Abstract
Pilocarpine, an important imidazole alkaloid, is extracted from the leaves of Pilocarpus microphyllus (Rutaceae), known in Brazil as jaborandi and used mainly for the treatment of glaucoma. Jaborandi leaves also contain other imidazole alkaloids, whose pharmacological and physiological properties are unknown, and whose
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Pilocarpine, an important imidazole alkaloid, is extracted from the leaves of Pilocarpus microphyllus (Rutaceae), known in Brazil as jaborandi and used mainly for the treatment of glaucoma. Jaborandi leaves also contain other imidazole alkaloids, whose pharmacological and physiological properties are unknown, and whose biosynthetic pathways are under investigation. In the present study, a HPLC method coupled with ESI-MSn was developed for their qualitative and quantitative analysis. This method permits the chromatographic separation of the imidazole alkaloids found in extracts of jaborandi, as well as the MS/MS analysis of the individual compounds. Thus two samples: leaves of P. microphyllus and a paste that is left over after the industrial extraction of pilocarpine; were compared. The paste was found to contain significant amounts of pilocarpine and other imidazole alkaloids, but had a slightly different alkaloid profile than the leaf extract. The method is suitable for the routine analysis of samples containing these alkaloids, as well as for the separation and identification of known and novel alkaloids from this family, and may be applied to further studies of the biosynthetic pathway of pilocarpine in P. microphyllus. Full article
(This article belongs to the Special Issue Alkaloids: Novel Therapeutic Perspectives)
Open AccessArticle Simplexidine, a 4-Alkylpyridinium Alkaloid from the Caribbean Sponge Plakortis simplex
Molecules 2008, 13(7), 1465-1471; doi:10.3390/molecules13071465
Received: 25 June 2008 / Accepted: 16 July 2008 / Published: 17 July 2008
Cited by 7 | PDF Full-text (205 KB) | HTML Full-text | XML Full-text
Abstract
Chemical analysis of the secondary metabolites of the Caribbean sponge Plakortis simplex, a source of many bioactive compounds, showed the presence of the new metabolite simplexidine (4), belonging to the extremely rare class of 4-alkyl-pyridinium alkaloids. The structural characterization of this molecule,
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Chemical analysis of the secondary metabolites of the Caribbean sponge Plakortis simplex, a source of many bioactive compounds, showed the presence of the new metabolite simplexidine (4), belonging to the extremely rare class of 4-alkyl-pyridinium alkaloids. The structural characterization of this molecule, based on spectroscopic methods, is reported. Full article
(This article belongs to the Special Issue Alkaloids: Novel Therapeutic Perspectives)
Open AccessArticle Effects of Anonaine on Dopamine Biosynthesis and L-DOPA-Induced Cytotoxicity in PC12 Cells
Molecules 2008, 13(2), 475-487; doi:10.3390/molecules13020475
Received: 30 January 2008 / Revised: 22 February 2008 / Accepted: 25 February 2008 / Published: 27 February 2008
Cited by 9 | PDF Full-text (141 KB) | HTML Full-text | XML Full-text
Abstract
The effects of anonaine, an aporphine isoquinoline alkaloid, on dopaminebiosynthesis and L-DOPA-induced cytotoxicity in PC12 cells were investigated. Anonaineat concentration ranges of 0.01-0.2 μM showed a significant inhibition of dopaminecontent at 24 h, with an IC50 value of 0.05 μM. Anonaine at
[...] Read more.
The effects of anonaine, an aporphine isoquinoline alkaloid, on dopaminebiosynthesis and L-DOPA-induced cytotoxicity in PC12 cells were investigated. Anonaineat concentration ranges of 0.01-0.2 μM showed a significant inhibition of dopaminecontent at 24 h, with an IC50 value of 0.05 μM. Anonaine at 0.05 μM inhibited tyrosinehydroxylase (TH) and aromatic L-amino acid decarboxylase (AADC) activities to 38.4-40.2% and 78.4-90.2% of control levels at 12-24 h and 3-6 h, respectively. TH activity wasmore influenced than AADC activity. Anonaine also decreased intracellular cyclic AMPlevels, but not intracellular Ca2+ concentrations. In addition, anonaine (0.05 μM) reducedL-DOPA (50 μM and 100 μM)-induced increases in dopamine content at 24 h. However,anonaine (0.05 μM) did not enhance L-DOPA (50 μM and 100 μM)-induced cell death 476after 24 h. These results suggest that anonaine inhibits dopamine biosynthesis by mainlyreducing TH activity without aggravating L-DOPA-induced cytotoxicity in PC12 cells. Full article
(This article belongs to the Special Issue Alkaloids: Novel Therapeutic Perspectives)
Open AccessCommunication NMR Spectra of Sparteine N1-oxide and α-Isosparteine N-oxide
Molecules 2008, 13(1), 3-10; doi:10.3390/molecules13010003
Received: 4 December 2007 / Accepted: 30 December 2007 / Published: 9 January 2008
Cited by 4 | PDF Full-text (83 KB) | HTML Full-text | XML Full-text
Abstract Sparteine N1-oxide and α-isosparteine N-oxide were prepared and theirstructures determined for the first time by 1H- and 13C-NMR spectroscopy using twodimensionaltechniques. The N-oxide effects were also calculated. Full article
(This article belongs to the Special Issue Alkaloids: Novel Therapeutic Perspectives)

Review

Jump to: Research

Open AccessReview Anti-Allergic Properties of Curine, a Bisbenzylisoquinoline Alkaloid
Molecules 2015, 20(3), 4695-4707; doi:10.3390/molecules20034695
Received: 31 October 2014 / Revised: 13 February 2015 / Accepted: 16 February 2015 / Published: 13 March 2015
Cited by 1 | PDF Full-text (1123 KB) | HTML Full-text | XML Full-text
Abstract
Curine is a bisbenzylisoquinoline alkaloid isolated from Chondrodendron platyphyllum (Menispermaceae). Recent findings have shed light on the actions of curine in different models of allergy and inflammation. Here we review the properties and mechanisms of action of curine focusing on its anti-allergic effects.
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Curine is a bisbenzylisoquinoline alkaloid isolated from Chondrodendron platyphyllum (Menispermaceae). Recent findings have shed light on the actions of curine in different models of allergy and inflammation. Here we review the properties and mechanisms of action of curine focusing on its anti-allergic effects. Curine pre-treatment significantly inhibited the scratching behavior, paw edema and systemic anaphylaxis induced by either ovalbumin (OVA) in sensitized animals or compound 48/80, through mechanisms of mast cell stabilization and inhibition of mast cell activation to generate lipid mediators. In addition, oral administration of curine significantly inhibited eosinophil recruitment and activation, as well as, OVA-induced airway hyper-responsiveness in a mouse model of asthma, through inhibition of the production of IL-13 and eotaxin, and of Ca2+ influx. In conclusion, curine exhibit anti-allergic effects in models of lung, skin and systemic allergy in the absence of significant toxicity, and as such has the potential for anti-allergic drug development. Full article
(This article belongs to the Special Issue Alkaloids: Novel Therapeutic Perspectives)
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Open AccessReview Indole Alkaloids from Catharanthus roseus: Bioproduction and Their Effect on Human Health
Molecules 2015, 20(2), 2973-3000; doi:10.3390/molecules20022973
Received: 30 October 2014 / Revised: 20 January 2015 / Accepted: 4 February 2015 / Published: 12 February 2015
Cited by 12 | PDF Full-text (811 KB) | HTML Full-text | XML Full-text
Abstract
Catharanthus roseus is a medicinal plant belonging to the family Apocynaceae which produces terpenoid indole alkaloids (TIAs) of high medicinal importance. Indeed, a number of activities like antidiabetic, bactericide and antihypertensive are linked to C. roseus. Nevertheless, the high added value of
[...] Read more.
Catharanthus roseus is a medicinal plant belonging to the family Apocynaceae which produces terpenoid indole alkaloids (TIAs) of high medicinal importance. Indeed, a number of activities like antidiabetic, bactericide and antihypertensive are linked to C. roseus. Nevertheless, the high added value of this plant is based on its enormous pharmaceutical interest, producing more than 130 TIAs, some of which exhibit strong pharmacological activities. The most striking biological activity investigated has been the antitumour effect of dimeric alkaloids such as anhydrovinblastine, vinblastine and vincristine which are already in pre-, clinical or in use. The great pharmacological importance of these indole alkaloids, contrasts with the small amounts of them found in this plant, making their extraction a very expensive process. To overcome this problem, researches have looked for alternative sources and strategies to produce them in higher amounts. In this sense, intensive research on the biosynthesis of TIAs and the regulation of their pathways has been developed with the aim to increase by biotechnological approaches, the production of these high added value compounds. This review is focused on the different strategies which improve TIA production, and in the analysis of the beneficial effects that these compounds exert on human health. Full article
(This article belongs to the Special Issue Alkaloids: Novel Therapeutic Perspectives)
Open AccessReview The Anti-Addiction Drug Ibogaine and the Heart: A Delicate Relation
Molecules 2015, 20(2), 2208-2228; doi:10.3390/molecules20022208
Received: 24 October 2014 / Revised: 11 November 2014 / Accepted: 26 November 2014 / Published: 29 January 2015
Cited by 6 | PDF Full-text (2025 KB) | HTML Full-text | XML Full-text
Abstract
The plant indole alkaloid ibogaine has shown promising anti-addictive properties in animal studies. Ibogaine is also anti-addictive in humans as the drug alleviates drug craving and impedes relapse of drug use. Although not licensed as therapeutic drug and despite safety concerns, ibogaine is
[...] Read more.
The plant indole alkaloid ibogaine has shown promising anti-addictive properties in animal studies. Ibogaine is also anti-addictive in humans as the drug alleviates drug craving and impedes relapse of drug use. Although not licensed as therapeutic drug and despite safety concerns, ibogaine is currently used as an anti-addiction medication in alternative medicine in dozens of clinics worldwide. In recent years, alarming reports of life-threatening complications and sudden death cases, temporally associated with the administration of ibogaine, have been accumulating. These adverse reactions were hypothesised to be associated with ibogaine’s propensity to induce cardiac arrhythmias. The aim of this review is to recapitulate the current knowledge about ibogaine’s effects on the heart and the cardiovascular system, and to assess the cardiac risks associated with the use of this drug in anti- addiction therapy. The actions of 18-methoxycoronaridine (18-MC), a less toxic ibogaine congener with anti-addictive properties, are also considered. Full article
(This article belongs to the Special Issue Alkaloids: Novel Therapeutic Perspectives)
Open AccessReview Activity of Alkaloids on Peptic Ulcer: What’s New?
Molecules 2015, 20(1), 929-950; doi:10.3390/molecules20010929
Received: 31 October 2014 / Accepted: 18 December 2014 / Published: 8 January 2015
Cited by 3 | PDF Full-text (733 KB) | HTML Full-text | XML Full-text
Abstract
Peptic ulcer is a common disease characterized by lesions that affect the mucosa of the esophagus, stomach and/or duodenum, and may extend into the muscular layer of the mucosa. Natural products have played an important role in the process of development and discovery
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Peptic ulcer is a common disease characterized by lesions that affect the mucosa of the esophagus, stomach and/or duodenum, and may extend into the muscular layer of the mucosa. Natural products have played an important role in the process of development and discovery of new drugs, due to their wide structural diversity and present, mostly specific and selective biological activities. Among natural products the alkaloids, biologically active secondary metabolites, that can be found in plants, animals or microorganisms stand out. The alkaloids are compounds consisting of a basic nitrogen atom that may or may not be part of a heterocyclic ring. This review will describe 15 alkaloids with antiulcer activity in animal models and in vitro studies. Full article
(This article belongs to the Special Issue Alkaloids: Novel Therapeutic Perspectives)
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Open AccessReview Alkaloids from Marine Invertebrates as Important Leads for Anticancer Drugs Discovery and Development
Molecules 2014, 19(12), 20391-20423; doi:10.3390/molecules191220391
Received: 14 October 2014 / Revised: 7 November 2014 / Accepted: 27 November 2014 / Published: 5 December 2014
Cited by 6 | PDF Full-text (972 KB) | HTML Full-text | XML Full-text
Abstract
The present review describes research on novel natural antitumor alkaloids isolated from marine invertebrates. The structure, origin, and confirmed cytotoxic activity of more than 130 novel alkaloids belonging to several structural families (indoles, pyrroles, pyrazines, quinolines, and pyridoacridines), together with some of their
[...] Read more.
The present review describes research on novel natural antitumor alkaloids isolated from marine invertebrates. The structure, origin, and confirmed cytotoxic activity of more than 130 novel alkaloids belonging to several structural families (indoles, pyrroles, pyrazines, quinolines, and pyridoacridines), together with some of their synthetic analogs, are illustrated. Recent discoveries concerning the current state of the potential and/or development of some of them as new drugs, as well as the current knowledge regarding their modes of action, are also summarized. A special emphasis is given to the role of marine invertebrate alkaloids as an important source of leads for anticancer drug discovery. Full article
(This article belongs to the Special Issue Alkaloids: Novel Therapeutic Perspectives)
Open AccessReview Alkaloids from the Tribe Bocconieae (Papaveraceae): A Chemical and Biological Review
Molecules 2014, 19(9), 13042-13060; doi:10.3390/molecules190913042
Received: 14 May 2014 / Accepted: 20 August 2014 / Published: 25 August 2014
Cited by 7 | PDF Full-text (836 KB) | HTML Full-text | XML Full-text
Abstract
The Bocconieae tribe, consisting of only the genera Macleaya and Bocconia, possesses significant economic and medicinal value and plays an important role in health management for people in developing countries. During the past decades, research on metabolites and relative pharmacology, including the
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The Bocconieae tribe, consisting of only the genera Macleaya and Bocconia, possesses significant economic and medicinal value and plays an important role in health management for people in developing countries. During the past decades, research on metabolites and relative pharmacology, including the isolation and identification of a variety of molecules, has shed light on the tribe. Among those molecules, isoquinoline alkaloids, and their antimicrobial, antifungal, and anti-inflammatory activities are especially noteworthy. This paper presents a comprehensive compilation of current research progress, with emphasis on the alkaloids and their distribution, phytochemical and pharmacological investigation, toxicity and side effects, related chemotaxonomy and future use prospects, and hopefully provides a valuable reference as an effort to promote further exploration and application of this tribe. Full article
(This article belongs to the Special Issue Alkaloids: Novel Therapeutic Perspectives)
Open AccessReview PM00104 (Zalypsis®): A Marine Derived Alkylating Agent
Molecules 2014, 19(8), 12328-12335; doi:10.3390/molecules190812328
Received: 25 July 2014 / Revised: 11 August 2014 / Accepted: 11 August 2014 / Published: 15 August 2014
Cited by 5 | PDF Full-text (657 KB) | HTML Full-text | XML Full-text
Abstract
PM00104 (Zalypsis®) is a synthethic tetrahydroisoquinolone alkaloid, which is structurally similar to many marine organisms. The compound has been proposed as a potential chemotherapeutic agent in the treatment of solid human tumors and hematological malignancies. PM00104 is a DNA binding agent,
[...] Read more.
PM00104 (Zalypsis®) is a synthethic tetrahydroisoquinolone alkaloid, which is structurally similar to many marine organisms. The compound has been proposed as a potential chemotherapeutic agent in the treatment of solid human tumors and hematological malignancies. PM00104 is a DNA binding agent, causing inhibition of the cell cycle and transcription, which can lead to double stranded DNA breaks. After rigorous pre-clinical testing, the drug has been evaluated in a number of phase II clinical trials. This manuscript provides a review of current trials and appraises the efficacy of PM00104 as a future cancer treatment. Full article
(This article belongs to the Special Issue Alkaloids: Novel Therapeutic Perspectives)
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Open AccessReview Berberine, an Epiphany Against Cancer
Molecules 2014, 19(8), 12349-12367; doi:10.3390/molecules190812349
Received: 27 June 2014 / Revised: 6 August 2014 / Accepted: 11 August 2014 / Published: 15 August 2014
Cited by 26 | PDF Full-text (1094 KB) | HTML Full-text | XML Full-text
Abstract
Alkaloids are used in traditional medicine for the treatment of many diseases. These compounds are synthesized in plants as secondary metabolites and have multiple effects on cellular metabolism. Among plant derivatives with biological properties, the isoquinoline quaternary alkaloid berberine possesses a broad range
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Alkaloids are used in traditional medicine for the treatment of many diseases. These compounds are synthesized in plants as secondary metabolites and have multiple effects on cellular metabolism. Among plant derivatives with biological properties, the isoquinoline quaternary alkaloid berberine possesses a broad range of therapeutic uses against several diseases. In recent years, berberine has been reported to inhibit cell proliferation and to be cytotoxic towards cancer cells. Based on this evidence, many derivatives have been synthesized to improve berberine efficiency and selectivity; the results so far obtained on human cancer cell lines support the idea that they could be promising agents for cancer treatment. The main properties of berberine and derivatives will be illustrated. Full article
(This article belongs to the Special Issue Alkaloids: Novel Therapeutic Perspectives)
Open AccessReview The Pharmacological Activities of (−)-Anonaine
Molecules 2013, 18(7), 8257-8263; doi:10.3390/molecules18078257
Received: 13 May 2013 / Revised: 28 June 2013 / Accepted: 3 July 2013 / Published: 12 July 2013
Cited by 5 | PDF Full-text (193 KB)
Abstract Several species of Magnoliaceae and Annonaceae are used in Traditional Chinese Medicine. (−)-Anonaine, isolated from several species of Magnoliaceae and Annonaceae, presents antiplasmodial, antibacterial, antifungal, antioxidation, anticancer, antidepression, and vasorelaxant activity. This article provides an overview of the pharmacological functions of (−)-anonaine. Full article
(This article belongs to the Special Issue Alkaloids: Novel Therapeutic Perspectives)
Open AccessReview Chromone and Flavonoid Alkaloids: Occurrence and Bioactivity
Molecules 2012, 17(1), 191-206; doi:10.3390/molecules17010191
Received: 9 November 2011 / Revised: 7 December 2011 / Accepted: 24 December 2011 / Published: 27 December 2011
Cited by 67 | PDF Full-text (259 KB)
Abstract
The chromone and flavonoid alkaloids represent an unusual group of structurally diverse secondary metabolites, derived from the convergence of multiple biosynthetic pathways that are widely distributed through the plant and animal kingdoms. Many of them have been discovered through bioassay-guided chemical investigations of
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The chromone and flavonoid alkaloids represent an unusual group of structurally diverse secondary metabolites, derived from the convergence of multiple biosynthetic pathways that are widely distributed through the plant and animal kingdoms. Many of them have been discovered through bioassay-guided chemical investigations of traditional medicines, suggesting potential therapeutic significance. Their unique structures and varied pharmacological activities may provide important new leads for the discovery of drugs with novel mechanisms of action. Potential therapeutic indications are as diverse as cancer and viral infections, inflammation and immunomodulation, neurological and psychiatric conditions, and diabetes. Full article
(This article belongs to the Special Issue Alkaloids: Novel Therapeutic Perspectives)
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Open AccessReview A Journey Under the Sea: The Quest for Marine Anti-Cancer Alkaloids
Molecules 2011, 16(11), 9665-9696; doi:10.3390/molecules16119665
Received: 24 October 2011 / Accepted: 9 November 2011 / Published: 23 November 2011
Cited by 45 | PDF Full-text (301 KB)
Abstract
The alarming increase in the global cancer death toll has fueled the quest for new effective anti-tumor drugs thorough biological screening of both terrestrial and marine organisms. Several plant-derived alkaloids are leading drugs in the treatment of different types of cancer and many
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The alarming increase in the global cancer death toll has fueled the quest for new effective anti-tumor drugs thorough biological screening of both terrestrial and marine organisms. Several plant-derived alkaloids are leading drugs in the treatment of different types of cancer and many are now being tested in various phases of clinical trials. Recently, marine-derived alkaloids, isolated from aquatic fungi, cyanobacteria, sponges, algae, and tunicates, have been found to also exhibit various anti-cancer activities including anti-angiogenic, anti-proliferative, inhibition of topoisomerase activities and tubulin polymerization, and induction of apoptosis and cytotoxicity. Two tunicate-derived alkaloids, aplidin and trabectedin, offer promising drug profiles, and are currently in phase II clinical trials against several solid and hematologic tumors. This review sheds light on the rich array of anti-cancer alkaloids in the marine ecosystem and introduces the most investigated compounds and their mechanisms of action. Full article
(This article belongs to the Special Issue Alkaloids: Novel Therapeutic Perspectives)
Open AccessReview Anti-Inflammatory Activity of Alkaloids: An Update from 2000 to 2010
Molecules 2011, 16(10), 8515-8534; doi:10.3390/molecules16108515
Received: 22 July 2011 / Revised: 7 September 2011 / Accepted: 26 September 2011 / Published: 11 October 2011
Cited by 29 | PDF Full-text (413 KB)
Abstract
Many natural substances with proven anti-inflammatory activity have been isolated throughout the years. The aim of this review is to review naturally sourced alkaloids with anti-inflammatory effects reported from 2000 to 2010. The assays were conducted mostly in vivo, and carrageenan-induced pedal
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Many natural substances with proven anti-inflammatory activity have been isolated throughout the years. The aim of this review is to review naturally sourced alkaloids with anti-inflammatory effects reported from 2000 to 2010. The assays were conducted mostly in vivo, and carrageenan-induced pedal edema was the most used experimental model. Of the 49 alkaloids evaluated, 40 demonstrated anti-inflammatory activity. Of these the most studied type were the isoquinolines. This review was based on NAPRALERT data bank, Web of Science and Chemical Abstracts. In this review, 95 references are cited. Full article
(This article belongs to the Special Issue Alkaloids: Novel Therapeutic Perspectives)
Open AccessReview The Potential of Tetrandrine as a Protective Agent for Ischemic Stroke
Molecules 2011, 16(9), 8020-8032; doi:10.3390/molecules16098020
Received: 25 August 2011 / Revised: 15 September 2011 / Accepted: 15 September 2011 / Published: 16 September 2011
Cited by 10 | PDF Full-text (368 KB)
Abstract
Stroke is one of the leading causes of mortality, with a high incidence of severe morbidity in survivors. The treatment to minimize tissue injury after stroke is still unsatisfactory and it is mandatory to develop effective treatment strategies for stroke. The pathophysiology of
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Stroke is one of the leading causes of mortality, with a high incidence of severe morbidity in survivors. The treatment to minimize tissue injury after stroke is still unsatisfactory and it is mandatory to develop effective treatment strategies for stroke. The pathophysiology of ischemic stroke is complex and involves many processes including energy failure, loss of ion homeostasis, increased intracellular calcium level, platelet aggregation, production of reactive oxygen species, disruption of blood brain barrier, and inflammation and leukocyte infiltration, etc. Tetrandrine, a bisbenzylisoquinoline alkaloid, has many pharmacologic effects including anti-inflammatory and cytoprotective effects. In addition, tetrandrine has been found to protect the liver, heart, small bowel and brain from ischemia/reperfusion injury. It is a calcium channel blocker, and can inhibit lipid peroxidation, reduce generation of reactive oxygen species, suppress the production of cytokines and inflammatory mediators, inhibit neutrophil recruitment and platelet aggregation, which are all devastating factors during ischemia/reperfusion injury of the brain. Because tetrandrine can counteract these important pathophysiological processes of ischemic stroke, it has the potential to be a protective agent for ischemic stroke. Full article
(This article belongs to the Special Issue Alkaloids: Novel Therapeutic Perspectives)
Open AccessReview Gastric and Duodenal Antiulcer Activity of Alkaloids: A Review
Molecules 2008, 13(12), 3198-3223; doi:10.3390/molecules13123198
Received: 30 July 2008 / Revised: 7 November 2008 / Accepted: 2 December 2008 / Published: 17 December 2008
Cited by 65 | PDF Full-text (183 KB) | HTML Full-text | XML Full-text
Abstract
Peptic ulcer disease is a deep gastrointestinal erosion disorder that involves the entire mucosal thickness and can even penetrate the muscular mucosa. Numerous natural products have been evaluated as therapeutics for the treatment of a variety of diseases, including this one. These products
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Peptic ulcer disease is a deep gastrointestinal erosion disorder that involves the entire mucosal thickness and can even penetrate the muscular mucosa. Numerous natural products have been evaluated as therapeutics for the treatment of a variety of diseases, including this one. These products usually derive from plant and animal sources that contain active constituents such as alkaloids, flavonoids, terpenoids, tannins and others. The alkaloids are natural nitrogen-containing secondary metabolites mostly derived from amino acids and found in about 20% of plants. There has been considerable pharmacological research into the antiulcer activity of these compounds. In this work we review the literature on alkaloids with antiulcer activity, which covers about sixty-one alkaloids, fifty-five of which have activity against this disease when induced in animals. Full article
(This article belongs to the Special Issue Alkaloids: Novel Therapeutic Perspectives)
Open AccessReview Rigorous Biogenetic Network for a Group of Indole Alkaloids Derived from Strictosidine
Molecules 2008, 13(8), 1875-1896; doi:10.3390/molecules13081875
Received: 5 August 2008 / Revised: 24 August 2008 / Accepted: 26 August 2008 / Published: 27 August 2008
Cited by 19 | PDF Full-text (410 KB) | HTML Full-text | XML Full-text
Abstract
Strictosidine, the precursor of more than 2,500 indole alkaloids, was isolated from four species of three plant families. By searching the Dictionary of Natural Products on DVD it was found that about 150 indole alkaloids were obtained from the same species (coalkaloids), which
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Strictosidine, the precursor of more than 2,500 indole alkaloids, was isolated from four species of three plant families. By searching the Dictionary of Natural Products on DVD it was found that about 150 indole alkaloids were obtained from the same species (coalkaloids), which is a direct proof of their common origin. On the base of their threedimensional structure, taxonomic properties and standard reaction mechanisms an extended network was established which involved the four fundamental skeletons, the three types of carbon framework in the secologanin subunit and all major groups of indole alkaloids derived from secologanin and tryptamine (except a few minor groups, in which only less then 10 alkaloids were known). The system was extended to the heterodimer indole alkaloids and the quinoindole alkaloids as well. Full article
(This article belongs to the Special Issue Alkaloids: Novel Therapeutic Perspectives)
Open AccessReview Application of Metabolic Engineering to the Production of Scopolamine
Molecules 2008, 13(8), 1722-1742; doi:10.3390/molecules13081722
Received: 3 June 2008 / Revised: 12 August 2008 / Accepted: 14 August 2008 / Published: 18 August 2008
Cited by 34 | PDF Full-text (1422 KB) | HTML Full-text | XML Full-text
Abstract
Scopolamine is an alkaloid widely used in medicine for its anticholinergic activity. The aim of this review is to show that metabolic engineering techniques constitute a suitable tool to improve the production of tropane alkaloids, focusing in particular on scopolamine. We present an
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Scopolamine is an alkaloid widely used in medicine for its anticholinergic activity. The aim of this review is to show that metabolic engineering techniques constitute a suitable tool to improve the production of tropane alkaloids, focusing in particular on scopolamine. We present an overview of results obtained by various research groups, including our own, who have studied the overexpression of genes involved in the biosynthesis of scopolamine in different plant species that produce tropane alkaloids. Experiments carried out to improve production in hairy root cultures will also be described, as well as those attempting to biotransform hyoscyamine into scopolamine in roots and transgenic tobacco cells. Full article
(This article belongs to the Special Issue Alkaloids: Novel Therapeutic Perspectives)
Open AccessReview Progress in the Studies on Rutaecarpine
Molecules 2008, 13(2), 272-300; doi:10.3390/molecules13020272
Received: 1 January 2008 / Revised: 1 February 2008 / Accepted: 2 February 2008 / Published: 6 February 2008
Cited by 55 | PDF Full-text (258 KB) | HTML Full-text | XML Full-text
Abstract
Rutaecarpine is an indolopyridoquinazolinone alkaloid isolated from Evodiarutaecarpa and related herbs, which has shown a variety of intriguing biological propertiessuch as anti-thrombotic, anticancer, anti-inflammatory and analgesic, anti-obesity andthermoregulatory, vasorelaxing activity, as well as effects on the cardiovascular andendocrine systems. Recent progress in the
[...] Read more.
Rutaecarpine is an indolopyridoquinazolinone alkaloid isolated from Evodiarutaecarpa and related herbs, which has shown a variety of intriguing biological propertiessuch as anti-thrombotic, anticancer, anti-inflammatory and analgesic, anti-obesity andthermoregulatory, vasorelaxing activity, as well as effects on the cardiovascular andendocrine systems. Recent progress in the studies on the isolation, synthesis, structureactivityrelationship studies, biological activities and metabolism of rutaecarpine arereviewed. Full article
(This article belongs to the Special Issue Alkaloids: Novel Therapeutic Perspectives)

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