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Special Issue in Honor of Professor James D. McChesney on the Occasion of his 80th Birthday

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

Deadline for manuscript submissions: closed (31 August 2021) | Viewed by 56038

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Guest Editor
National Center for Natural Products Research, Research Institute of Pharmaceutical Sciences, School of Pharmacy, Thad Cochran Research Center, University of Mississippi, University, MS 38677, USA
Interests: isolation and structure elucidation of antiinfective; anticancer; chemopreventive; neuroprotective and agrochemical constituents from plants and their use in human and plant health
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Guest Editor
National Center for Natural Products Research, Research Institute of Pharmaceutical Sciences, School of Pharmacy, Thad Cochran Research Center, University of Mississippi, University, MS 38677, USA
Interests: isolation and structure elucidation of biologically active compounds from natural sources and optimization of therapeutic index of lead compounds by chemical modifications

Special Issue Information

Dear Colleague,

text

Dr. James D. McChesney

Higher plants and their products have been used as food, medicine, agrochemicals, food preservatives, flavoring agents, and spices since the dawn of the human civilization. More recently, they have been the sources of important pharmaceuticals to combat a number of diseases. The antimalarial drugs artemisinin and quinine, the anticancer drugs taxol, etoposide, and vinca alkalods, and the sugar-free sweetening agents stevioside and rebaudiosides are good examples of important plant-based drugs and food additives currently on the market. In spite of these and many other successes, there are significant challenges to discovering and developing commercially important natural products from plants. Often, active natural products have complex molecular structures with multiple asymmetric centers, and isolating them from natural sources remains the only economical way of obtaining them in sufficient quantities to carry out development studies. However, due to ecological and environmental reasons, procuring plant materials in large quantities has become quite difficult, and the separation of active constituents from complex mixtures can be challenging. Furthermore, due to undesirable qualities, such as low solubility or poor chemical or metabolic stability, active constituents may be nonviable as commercial products.

Dr. James D. McChesney, who is a firm believer in the tremendous potential of higher plants as sources for drugs, agrochemicals, and food additives, has contributed immensely to overcoming these challenges in order to bring nature-based products to market. His work has focused on searching for plant strains with a high content of active compounds, particularly in plant parts such as leaves so they can be harvested in sustainable manner, as well as micropropagating these strains to mass produce plants with uniform chemical profiles rapidly. Additionally, he has developed practical, efficient, and economical separation methods to isolate active compounds on a large scale and has used chemical modification of active constituents to improve bioavailability and therapeutic index. His research on artemisinin, taxol, galanthamine, podophyllotoxin, and stevia sweet glycosides exemplifies the magnitude of his contributions.  His extensive work on the structural modification of taxol led to the discovery and development of the anticancer agent TPI 287, a third generation taxane analog which is currently undergoing clinical trials.

In addition to his contributions to natural product-based drug development, for more than 40 years, he was involved in the development of 8-aminoquinoline antimalarials, the only group of compounds currently available for the treatment of relapsing malaria. His efforts in this area led to a broader understanding of the mechanism of activity and toxicity of this class of compounds, and resulted in the development of NPC1161B, a drug candidate which is not only active against all stages of the life cycle of plasmodium in humans, but also highly effective in the treatment of leishmaniasis and Pneumocystis pneumonia. This compound is currently undergoing preclinical development.

As a further example of his dedication to advancing natural products research, Dr. McChesney was instrumental in obtaining grant money from the United States Department of Agriculture to establish the National Center for Natural Products Research at the University of Mississippi, a research facility shared with the Natural Products Utilization Research Unit of the Agricultural Research Service of the USDA to carry out discovery and development of natural product-based pharmaceuticals and agrochemicals.

Dr. James D. McChesney was born near Hatfield, a small town in Missouri, in 1939 and completed a BSc in chemical technology from Iowa State University in 1961. In 1964, he received an MA in botany from the University of Indiana, and, in the following year, he received a PhD in organic chemistry from the same institution. Soon after, he joined the Department of Botany and later the School of Pharmacy at the University of Kansas and became a Professor of Botany and Medicinal Chemistry. In 1978, he joined the Department of Pharmacognosy in the School of Pharmacy at The University of Mississippi as the Chair of the department and became the Director of the Research Institute of Pharmaceutical Science in 1986. In 1996, he joined NaPro Bio Therapeutics in Boulder, Colorado as the Vice President of Development. He became the chief scientific officer of Tapestry Pharmaceuticals and then ChromaDex of Boulder, Colorado in 2003. He moved back to his farm home near Etta, Mississippi in 2009 and founded his own companies (Ironstone Separations, Arbor Therapeutics, and Cloaked Therapeutics) to pursue his interest in commercial development of natural products.

Now semi-retired and back at his farm in Oxford, Mississippi, he is pursuing his passion for research in this area, is still involved in the commercial development of natural product-based pharmaceuticals, and participates in research group meetings at the University of Mississippi, where he serves as an adjunct faculty.

Dr. McChesney has had a long, distinguished teaching and research career, has authored more than 225 research publications, and holds more than 60 patents. He is a past president and a fellow of the American Society of Pharmacognosy and a Fellow of the AAAS. He has mentored many graduate students, post-docs, and junior faculty members who hold prominent positions in natural products research establishments in the US and around the world.

We are honored to organize this Special Issue to celebrate Dr. McChesney’s 80th birthday and to dedicate this issue to his enormous contributions to natural products research and development. We welcome manuscripts in the areas of natural product drug discovery, dietary supplements, analytical methodology, synthesis, and agrochemicals from the academic, scientific, and research communities.

Prof. Dr. Muhammad Ilias
Prof. Dr. Dhammika Nanayakkara
Guest Editor

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Published Papers (17 papers)

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Editorial

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5 pages, 442 KiB  
Editorial
Special Issue: “James D. McChesney, Vision, Passion and Leadership in the Development of Plant-Derived Natural Products”
by Larry A. Walker and N. P. Dhammika Nanayakkara
Molecules 2021, 26(24), 7415; https://doi.org/10.3390/molecules26247415 - 07 Dec 2021
Viewed by 1778
Abstract
It is a distinct pleasure for me to offer something in recognition of and tribute to Dr [...] Full article
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Research

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13 pages, 3664 KiB  
Article
Glycyrrhizic Acid Inhibits SARS-CoV-2 Infection by Blocking Spike Protein-Mediated Cell Attachment
by Jingjing Li, Dongge Xu, Lingling Wang, Mengyu Zhang, Guohai Zhang, Erguang Li and Susu He
Molecules 2021, 26(20), 6090; https://doi.org/10.3390/molecules26206090 - 09 Oct 2021
Cited by 32 | Viewed by 4103
Abstract
Glycyrrhizic acid (GA), also known as glycyrrhizin, is a triterpene glycoside isolated from plants of Glycyrrhiza species (licorice). GA possesses a wide range of pharmacological and antiviral activities against enveloped viruses including severe acute respiratory syndrome (SARS) virus. Since the S protein (S) [...] Read more.
Glycyrrhizic acid (GA), also known as glycyrrhizin, is a triterpene glycoside isolated from plants of Glycyrrhiza species (licorice). GA possesses a wide range of pharmacological and antiviral activities against enveloped viruses including severe acute respiratory syndrome (SARS) virus. Since the S protein (S) mediates SARS coronavirus 2 (SARS-CoV-2) cell attachment and cell entry, we assayed the GA effect on SARS-CoV-2 infection using an S protein-pseudotyped lentivirus (Lenti-S). GA treatment dose-dependently blocked Lenti-S infection. We showed that incubation of Lenti-S virus, but not the host cells with GA prior to the infection, reduced Lenti-S infection, indicating that GA targeted the virus for infection. Surface plasmon resonance measurement showed that GA interacted with a recombinant S protein and blocked S protein binding to host cells. Autodocking analysis revealed that the S protein has several GA-binding pockets including one at the interaction interface to the receptor angiotensin-converting enzyme 2 (ACE2) and another at the inner side of the receptor-binding domain (RBD) which might impact the close-to-open conformation change of the S protein required for ACE2 interaction. In addition to identifying GA antiviral activity against SARS-CoV-2, the study linked GA antiviral activity to its effect on virus cell binding. Full article
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10 pages, 1032 KiB  
Article
Development of UHPLC/Q-TOF Analysis Method to Screen Glycerin for Direct Detection of Process Contaminants 3-Monochloropropane-1,2-diol Esters (3-MCPDEs) and Glycidyl Esters (GEs)
by Lauren Girard, Kithsiri Herath, Hernando Escobar, Renate Reimschuessel, Olgica Ceric and Hiranthi Jayasuriya
Molecules 2021, 26(9), 2449; https://doi.org/10.3390/molecules26092449 - 22 Apr 2021
Cited by 6 | Viewed by 2092
Abstract
The U.S. Food and Drug Administration’s (FDA′s) Center for Veterinary Medicine (CVM) has been investigating reports of pets becoming ill after consuming jerky pet treats since 2007. Renal failure accounted for 30% of reported cases. Jerky pet treats contain glycerin, which can be [...] Read more.
The U.S. Food and Drug Administration’s (FDA′s) Center for Veterinary Medicine (CVM) has been investigating reports of pets becoming ill after consuming jerky pet treats since 2007. Renal failure accounted for 30% of reported cases. Jerky pet treats contain glycerin, which can be made from vegetable oil or as a byproduct of biodiesel production. Glycidyl esters (GEs) and 3-monochloropropanediol esters (3-MCPDEs) are food contaminants that can form in glycerin during the refining process. 3-MCPDEs and GEs pose food safety concerns, as they can release free 3-MCPD and glycidol in vivo. Evidence from studies in animals shows that 3-MCPDEs are potential toxins with kidneys as their main target. As renal failure accounted for 30% of reported pet illnesses after the consumption of jerky pet treats containing glycerin, there is a need to develop a screening method to detect 3-MCPDEs and GEs in glycerin. We describe the development of an ultra-high-pressure liquid chromatography/quadrupole time-of-flight (UHPLC/Q-TOF) method for screening glycerin for MCPDEs and GEs. Glycerin was extracted and directly analyzed without a solid-phase extraction procedure. An exact mass database, developed in-house, of MCPDEs and GEs formed with common fatty acids was used in the screening. Full article
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18 pages, 2662 KiB  
Article
Anti-Inflammatory, Antidiabetic Properties and In Silico Modeling of Cucurbitane-Type Triterpene Glycosides from Fruits of an Indian Cultivar of Momordica charantia L.
by Wilmer H. Perera, Siddanagouda R. Shivanagoudra, Jose L. Pérez, Da Mi Kim, Yuxiang Sun, Guddadarangavvanahally K. Jayaprakasha and Bhimanagouda S. Patil
Molecules 2021, 26(4), 1038; https://doi.org/10.3390/molecules26041038 - 16 Feb 2021
Cited by 24 | Viewed by 3086
Abstract
Diabetes mellitus is a chronic disease and one of the fastest-growing health challenges of the last decades. Studies have shown that chronic low-grade inflammation and activation of the innate immune system are intimately involved in type 2 diabetes pathogenesis. Momordica charantia L. fruits [...] Read more.
Diabetes mellitus is a chronic disease and one of the fastest-growing health challenges of the last decades. Studies have shown that chronic low-grade inflammation and activation of the innate immune system are intimately involved in type 2 diabetes pathogenesis. Momordica charantia L. fruits are used in traditional medicine to manage diabetes. Herein, we report the purification of a new 23-O-β-d-allopyranosyl-5β,19-epoxycucurbitane-6,24-diene triterpene (charantoside XV, 6) along with 25ξ-isopropenylchole-5(6)-ene-3-O-β-d-glucopyranoside (1), karaviloside VI (2), karaviloside VIII (3), momordicoside L (4), momordicoside A (5) and kuguaglycoside C (7) from an Indian cultivar of Momordica charantia. At 50 µM compounds, 26 differentially affected the expression of pro-inflammatory markers IL-6, TNF-α, and iNOS, and mitochondrial marker COX-2. Compounds tested for the inhibition of α-amylase and α-glucosidase enzymes at 0.87 mM and 1.33 mM, respectively. Compounds showed similar α-amylase inhibitory activity than acarbose (0.13 mM) of control (68.0–76.6%). Karaviloside VIII (56.5%) was the most active compound in the α-glucosidase assay, followed by karaviloside VI (40.3%), while momordicoside L (23.7%), A (33.5%), and charantoside XV (23.9%) were the least active compounds. To better understand the mode of binding of cucurbitane-triterpenes to these enzymes, in silico docking of the isolated compounds was evaluated with α-amylase and α-glucosidase. Full article
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11 pages, 2521 KiB  
Article
Antimalarials and Phytotoxins from Botryosphaeria dothidea Identified from a Seed of Diseased Torreya taxifolia
by Mallika Kumarihamy, Luiz H. Rosa, Natascha Techen, Daneel Ferreira, Edward M. Croom, Jr., Stephen O. Duke, Babu L. Tekwani, Shabana Khan and N. P. Dhammika Nanayakkara
Molecules 2021, 26(1), 59; https://doi.org/10.3390/molecules26010059 - 24 Dec 2020
Cited by 9 | Viewed by 2218
Abstract
The metabolic pathways in the apicoplast organelle of Plasmodium parasites are similar to those in plastids in plant cells and are suitable targets for malaria drug discovery. Some phytotoxins released by plant pathogenic fungi have been known to target metabolic pathways of the [...] Read more.
The metabolic pathways in the apicoplast organelle of Plasmodium parasites are similar to those in plastids in plant cells and are suitable targets for malaria drug discovery. Some phytotoxins released by plant pathogenic fungi have been known to target metabolic pathways of the plastid; thus, they may also serve as potential antimalarial drug leads. An EtOAc extract of the broth of the endophyte Botryosphaeria dothidea isolated from a seed collected from a Torreya taxifolia plant with disease symptoms, showed in vitro antimalarial and phytotoxic activities. Bioactivity-guided fractionation of the extract afforded a mixture of two known isomeric phytotoxins, FRT-A and flavipucine (or their enantiomers, sapinopyridione and (-)-flavipucine), and two new unstable γ-lactam alkaloids dothilactaenes A and B. The isomeric mixture of phytotoxins displayed strong phytotoxicity against both a dicot and a monocot and moderate cytotoxicity against a panel of cell lines. Dothilactaene A showed no activity. Dothilactaene B was isolated from the active fraction, which showed moderate in vitro antiplasmodial activity with high selectivity index. In spite of this activity, its instability and various other biological activities shown by related compounds would preclude it from being a viable antimalarial lead. Full article
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14 pages, 1729 KiB  
Article
Antimicrobial Constituents from Machaerium Pers.: Inhibitory Activities and Synergism of Machaeriols and Machaeridiols against Methicillin-Resistant Staphylococcus aureus, Vancomycin-Resistant Enterococcus faecium, and Permeabilized Gram-Negative Pathogens
by Ilias Muhammad, Melissa R. Jacob, Mohamed A. Ibrahim, Vijayasankar Raman, Mallika Kumarihamy, Mei Wang, Taha Al-Adhami, Charlotte Hind, Melanie Clifford, Bethany Martin, Jianping Zhao, J. Mark Sutton and Khondaker Miraz Rahman
Molecules 2020, 25(24), 6000; https://doi.org/10.3390/molecules25246000 - 18 Dec 2020
Cited by 8 | Viewed by 2444
Abstract
Two new epimeric bibenzylated monoterpenes machaerifurogerol (1a) and 5-epi-machaerifurogerol (1b), and four known isoflavonoids (+)-vestitol (2), 7-O-methylvestitol (3), (+)-medicarpin (4), and 3,8-dihydroxy-9-methoxypterocarpan (5) were isolated from Machaerium [...] Read more.
Two new epimeric bibenzylated monoterpenes machaerifurogerol (1a) and 5-epi-machaerifurogerol (1b), and four known isoflavonoids (+)-vestitol (2), 7-O-methylvestitol (3), (+)-medicarpin (4), and 3,8-dihydroxy-9-methoxypterocarpan (5) were isolated from Machaerium Pers. This plant was previously assigned as Machaerium multiflorum Spruce, from which machaeriols A-D (69) and machaeridiols A-C (1012) were reported, and all were then re-isolated, except the minor compound 9, for a comprehensive antimicrobial activity evaluation. Structures of the isolated compounds were determined by full NMR and mass spectroscopic data. Among the isolated compounds, the mixture 10 + 11 was the most active with an MIC value of 1.25 μg/mL against methicillin-resistant Staphylococcus aureus (MRSA) strains BAA 1696, −1708, −1717, −33591, and vancomycin-resistant Enterococcus faecium (VRE 700221) and E. faecalis (VRE 51299) and vancomycin-sensitive E. faecalis (VSE 29212). Compounds 68 and 1012 were found to be more potent against MRSA 1708, and 6, 11, and 12 against VRE 700221, than the drug control ciprofloxacin and vancomycin. A combination study using an in vitro Checkerboard method was carried out for machaeriols (7 or 8) and machaeridiols (11 or 12), which exhibited a strong synergistic activity of 12 + 8 (MIC 0.156 and 0.625 µg/mL), with >32- and >8-fold reduction of MIC’s, compared to 12, against MRSA 1708 and −1717, respectively. In the presence of sub-inhibitory concentrations on polymyxin B nonapeptide (PMBN), compounds 10 + 11, 11, 12, and 8 showed activity in the range of 0.5–8 µg/mL for two strains of Acinetobacter baumannii, 2–16 µg/mL against Pseudomonas aeruginosa PAO1, and 2 µg/mL against Escherichia coli NCTC 12923, but were inactive (MIC > 64 µg/mL) against the two isolates of Klebsiella pneumoniae. Full article
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12 pages, 573 KiB  
Article
Newly Generated Atractylon Derivatives in Processed Rhizomes of Atractylodes macrocephala Koidz
by Chunmei Zhai, Jianping Zhao, Amar G. Chittiboyina, Yonghai Meng, Mei Wang and Ikhlas A. Khan
Molecules 2020, 25(24), 5904; https://doi.org/10.3390/molecules25245904 - 13 Dec 2020
Cited by 8 | Viewed by 2483
Abstract
Thermally processed rhizomes of Atractylodes macrocephala (RAM) have a long history of use in traditional Chinese medicine (TCM) for treating various disorders, and have been an integral part of various traditional drugs and healthcare products. In TCM, herbal medicines are, in most cases, [...] Read more.
Thermally processed rhizomes of Atractylodes macrocephala (RAM) have a long history of use in traditional Chinese medicine (TCM) for treating various disorders, and have been an integral part of various traditional drugs and healthcare products. In TCM, herbal medicines are, in most cases, uniquely processed. Although it is thought that processing can alter the properties of herbal medicines so as to achieve desired functions, increase potency, and/or reduce side effects, the underlying chemical changes remain unclear for most thermally processed Chinese herbal medicines. In an attempt to shed some light on the scientific rationale behind the processes involved in traditional medicine, the RAM processed by stir-frying with wheat bran was investigated for the change of chemical composition. As a result, for the first time, five new chemical entities, along with ten known compounds, were isolated. Their chemical structures were determined by spectroscopic and spectrometric analyses. The possible synthetic pathway for the generation of such thermally-induced chemical entities was also proposed. Furthermore, biological activity evaluation showed that none of the compounds possessed cytotoxic effects against the tested mammalian cancer and noncancer cell lines. In addition, all compounds were ineffective at inhibiting the growth of the pathogenic microorganisms. Full article
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14 pages, 3306 KiB  
Article
Selective Interactions of O-Methylated Flavonoid Natural Products with Human Monoamine Oxidase-A and -B
by Narayan D. Chaurasiya, Jacob Midiwo, Pankaj Pandey, Regina N. Bwire, Robert J. Doerksen, Ilias Muhammad and Babu L. Tekwani
Molecules 2020, 25(22), 5358; https://doi.org/10.3390/molecules25225358 - 17 Nov 2020
Cited by 10 | Viewed by 2610
Abstract
A set of structurally related O-methylated flavonoid natural products isolated from Senecio roseiflorus (1), Polygonum senegalense (2 and 3), Bhaphia macrocalyx (4), Gardenia ternifolia (5), and Psiadia punctulata (6) plant species were [...] Read more.
A set of structurally related O-methylated flavonoid natural products isolated from Senecio roseiflorus (1), Polygonum senegalense (2 and 3), Bhaphia macrocalyx (4), Gardenia ternifolia (5), and Psiadia punctulata (6) plant species were characterized for their interaction with human monoamine oxidases (MAO-A and -B) in vitro. Compounds 1, 2, and 5 showed selective inhibition of MAO-A, while 4 and 6 showed selective inhibition of MAO-B. Compound 3 showed ~2-fold selectivity towards inhibition of MAO-A. Binding of compounds 13 and 5 with MAO-A, and compounds 3 and 6 with MAO-B was reversible and not time-independent. The analysis of enzyme-inhibition kinetics suggested a reversible-competitive mechanism for inhibition of MAO-A by 1 and 3, while a partially-reversible mixed-type inhibition by 5. Similarly, enzyme inhibition-kinetics analysis with compounds 3, 4, and 6, suggested a competitive reversible inhibition of MAO-B. The molecular docking study suggested that 1 selectively interacts with the active-site of human MAO-A near N5 of FAD. The calculated binding free energies of the O-methylated flavonoids (1 and 46) and chalcones (2 and 3) to MAO-A matched closely with the trend in the experimental IC50′s. Analysis of the binding free-energies suggested better interaction of 4 and 6 with MAO-B than with MAO-A. The natural O-methylated flavonoid (1) with highly potent inhibition (IC50 33 nM; Ki 37.9 nM) and >292 fold selectivity against human MAO-A (vs. MAO-B) provides a new drug lead for the treatment of neurological disorders. Full article
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10 pages, 1335 KiB  
Article
Teratopyrones A–C, Dimeric Naphtho-γ-Pyrones and Other Metabolites from Teratosphaeria sp. AK1128, a Fungal Endophyte of Equisetum arvense
by Ya-Ming Xu, A. Elizabeth Arnold, Jana M. U′Ren, Li-Jiang Xuan, Wen-Qiong Wang and A. A. Leslie Gunatilaka
Molecules 2020, 25(21), 5058; https://doi.org/10.3390/molecules25215058 - 30 Oct 2020
Cited by 1 | Viewed by 2178
Abstract
Bioassay-guided fractionation of a cytotoxic extract derived from a solid potato dextrose agar (PDA) culture of Teratosphaeria sp. AK1128, a fungal endophyte of Equisetum arvense, afforded three new naphtho-γ-pyrone dimers, teratopyrones A–C (13), together with five known naphtho-γ-pyrones, [...] Read more.
Bioassay-guided fractionation of a cytotoxic extract derived from a solid potato dextrose agar (PDA) culture of Teratosphaeria sp. AK1128, a fungal endophyte of Equisetum arvense, afforded three new naphtho-γ-pyrone dimers, teratopyrones A–C (13), together with five known naphtho-γ-pyrones, aurasperone B (4), aurasperone C (5), aurasperone F (6), nigerasperone A (7), and fonsecin B (8), and two known diketopiperazines, asperazine (9) and isorugulosuvine (10). The structures of 13 were determined on the basis of their spectroscopic data. Cytotoxicity assay revealed that nigerasperone A (7) was moderately active against the cancer cell lines PC-3M (human metastatic prostate cancer), NCI-H460 (human non-small cell lung cancer), SF-268 (human CNS glioma), and MCF-7 (human breast cancer), with IC50s ranging from 2.37 to 4.12 μM while other metabolites exhibited no cytotoxic activity up to a concentration of 5.0 μM. Full article
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8 pages, 1995 KiB  
Communication
Oxyresveratrol Possesses DNA Damaging Activity
by Sarayut Radapong, Satyajit D. Sarker and Kenneth J. Ritchie
Molecules 2020, 25(11), 2577; https://doi.org/10.3390/molecules25112577 - 01 Jun 2020
Cited by 9 | Viewed by 2430
Abstract
Artocarpus lakoocha Wall. ex Roxb. (family: Moraceae) has been used as a traditional Thai medicine for the treatment of various parasitic diseases. This species has been reported to be the source of phytochemicals, which show potent biological activities. The objective of this [...] Read more.
Artocarpus lakoocha Wall. ex Roxb. (family: Moraceae) has been used as a traditional Thai medicine for the treatment of various parasitic diseases. This species has been reported to be the source of phytochemicals, which show potent biological activities. The objective of this study was to investigate the phytochemical profile of the extracts of the heartwood of A. lakoocha and their pro-oxidant activity in vitro. The heartwood was ground, extracted, and then chromatographic and spectroscopic analyses were carried out; oxyresveratrol was identified as the major component in the extracts. The pro-oxidant activity was investigated using DNA-nick, reactive oxygen species and reducing assays. The results showed that oxyresveratrol induced DNA damage dose-dependently in the presence of copper (II) ions. It was also found to generate reactive oxygen species (ROS) in a dose-dependent manner and reduce copper (II) to copper (I). It is concluded that oxyresveratrol is the most abundant stilbenoid in A. lakoocha heartwood. The compound exhibited pro-oxidant activity in the presence of copper (II) ions, which may be associated with its ability to act as an anticancer compound. Full article
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7 pages, 885 KiB  
Communication
Dalbergia ecastaphyllum (L.) Taub. and Symphonia globulifera L.f.: The Botanical Sources of Isoflavonoids and Benzophenones in Brazilian Red Propolis
by Gari Vidal Ccana-Ccapatinta, Jennyfer Andrea Aldana Mejía, Matheus Hikaru Tanimoto, Milton Groppo, Jean Carlos Andrade Sarmento de Carvalho and Jairo Kenupp Bastos
Molecules 2020, 25(9), 2060; https://doi.org/10.3390/molecules25092060 - 28 Apr 2020
Cited by 41 | Viewed by 3881
Abstract
The Brazilian red propolis (BRP) constitutes an important commercial asset for northeast Brazilian beekeepers. The role of Dalbergia ecastaphyllum (L.) Taub. (Fabaceae) as the main botanical source of this propolis has been previously confirmed. However, in addition to isoflavonoids and other phenolics, which [...] Read more.
The Brazilian red propolis (BRP) constitutes an important commercial asset for northeast Brazilian beekeepers. The role of Dalbergia ecastaphyllum (L.) Taub. (Fabaceae) as the main botanical source of this propolis has been previously confirmed. However, in addition to isoflavonoids and other phenolics, which are present in the resin of D. ecastaphyllum, samples of BRP are reported to contain substantial amounts of polyprenylated benzophenones, whose botanical source was unknown. Therefore, field surveys, phytochemical and chromatographic analyses were undertaken to confirm the botanical sources of the red propolis produced in apiaries located in Canavieiras, Bahia, Brazil. The results confirmed D. ecastaphyllum as the botanical source of liquiritigenin (1), isoliquiritigenin (2), formononetin (3), vestitol (4), neovestitol (5), medicarpin (6), and 7-O-neovestitol (7), while Symphonia globulifera L.f. (Clusiaceae) is herein reported for the first time as the botanical source of polyprenylated benzophenones, mainly guttiferone E (8) and oblongifolin B (9), as well as the triterpenoids β-amyrin (10) and glutinol (11). The chemotaxonomic and economic significance of the occurrence of polyprenylated benzophenones in red propolis is discussed. Full article
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19 pages, 1724 KiB  
Article
Co-Loaded Curcumin and Methotrexate Nanocapsules Enhance Cytotoxicity against Non-Small-Cell Lung Cancer Cells
by Loanda Aparecida Cabral Rudnik, Paulo Vitor Farago, Jane Manfron Budel, Amanda Lyra, Fernanda Malaquias Barboza, Traudi Klein, Carla Cristine Kanunfre, Jessica Mendes Nadal, Matheus Coelho Bandéca, Vijayasankar Raman, Andressa Novatski, Alessandro Dourado Loguércio and Sandra Maria Warumby Zanin
Molecules 2020, 25(8), 1913; https://doi.org/10.3390/molecules25081913 - 21 Apr 2020
Cited by 16 | Viewed by 3200
Abstract
Background: As part of the efforts to find natural alternatives for cancer treatment and to overcome the barriers of cellular resistance to chemotherapeutic agents, polymeric nanocapsules containing curcumin and/or methotrexate were prepared by an interfacial deposition of preformed polymer method. Methods: [...] Read more.
Background: As part of the efforts to find natural alternatives for cancer treatment and to overcome the barriers of cellular resistance to chemotherapeutic agents, polymeric nanocapsules containing curcumin and/or methotrexate were prepared by an interfacial deposition of preformed polymer method. Methods: Physicochemical properties, drug release experiments and in vitro cytotoxicity of these nanocapsules were performed against the Calu-3 lung cancer cell line. Results: The colloidal suspensions of nanocapsules showed suitable size (287 to 325 nm), negative charge (−33 to −41 mV) and high encapsulation efficiency (82.4 to 99.4%). Spherical particles at nanoscale dimensions were observed by scanning electron microscopy. X-ray diffraction analysis indicated that nanocapsules exhibited a non-crystalline pattern with a remarkable decrease of crystalline peaks of the raw materials. Fourier-transform infrared spectra demonstrated no chemical bond between the drug(s) and polymers. Drug release experiments evidenced a controlled release pattern with no burst effect for nanocapsules containing curcumin and/or methotrexate. The nanoformulation containing curcumin and methotrexate (NCUR/MTX-2) statistically decreased the cell viability of Calu-3. The fluorescence and morphological analyses presented a predominance of early apoptosis and late apoptosis as the main death mechanisms for Calu-3. Conclusions: Curcumin and methotrexate co-loaded nanocapsules can be further used as a novel therapeutic strategy for treating non-small-cell lung cancer. Full article
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17 pages, 1426 KiB  
Article
Characterization, Quantification and Quality Assessment of Avocado (Persea americana Mill.) Oils
by Mei Wang, Ping Yu, Amar G. Chittiboyina, Dilu Chen, Jianping Zhao, Bharathi Avula, Yan-Hong Wang and Ikhlas A. Khan
Molecules 2020, 25(6), 1453; https://doi.org/10.3390/molecules25061453 - 24 Mar 2020
Cited by 19 | Viewed by 4855
Abstract
Avocado oil is prized for its high nutritional value due to the substantial amounts of triglycerides (TGs) and unsaturated fatty acids (FAs) present. While avocado oil is traditionally extracted from mature fruit flesh, alternative sources such as avocado seed oil have recently increased [...] Read more.
Avocado oil is prized for its high nutritional value due to the substantial amounts of triglycerides (TGs) and unsaturated fatty acids (FAs) present. While avocado oil is traditionally extracted from mature fruit flesh, alternative sources such as avocado seed oil have recently increased in popularity. Unfortunately, sufficient evidence is not available to support the claimed health benefit and safe use of such oils. To address potential quality issues and identify possible adulteration, authenticated avocado oils extracted from the fruit peel, pulp and seed by supercritical fluid extraction (SFE), as well as commercial avocado pulp and seed oils sold in US market were analyzed for TGs and FAs in the present study. Characterization and quantification of TGs were conducted using UHPLC/ESI-MS. Thirteen TGs containing saturated and unsaturated fatty acids in avocado oils were unambiguously identified. Compared to traditional analytical methods, which are based only on the relative areas of chromatographic peaks neglecting the differences in the relative response of individual TG, our method improved the quantification of TGs by using the reference standards whenever possible or the reference standards with the same equivalent carbon number (ECN). To verify the precision and accuracy of the UHPLC/ESI-MS method, the hydrolysis and transesterification products of avocado oil were analyzed for fatty acid methyl esters using a GC/MS method. The concentrations of individual FA were calculated, and the results agreed with the UHPLC/ESI-MS method. Although chemical profiles of avocado oils from pulp and peel are very similar, a significant difference was observed for the seed oil. Principal component analysis (PCA) based on TG and FA compositional data allowed correct identification of individual avocado oil and detection of possible adulteration. Full article
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13 pages, 3330 KiB  
Article
Insecticidal and Biting Deterrent Activities of Magnolia grandiflora Essential Oils and Selected Pure Compounds against Aedes aegypti
by Abbas Ali, Nurhayat Tabanca, Betul Demirci, Vijayasankar Raman, Jane M. Budel, K. Hüsnü Can Baser and Ikhlas A. Khan
Molecules 2020, 25(6), 1359; https://doi.org/10.3390/molecules25061359 - 17 Mar 2020
Cited by 19 | Viewed by 3838
Abstract
In our natural products screening program for mosquitoes, we tested essential oils extracted from different plant parts of Magnolia grandiflora L. for their insecticidal and biting deterrent activities against Aedes aegypti. Biting deterrence of seeds essential oil with biting deterrence index value [...] Read more.
In our natural products screening program for mosquitoes, we tested essential oils extracted from different plant parts of Magnolia grandiflora L. for their insecticidal and biting deterrent activities against Aedes aegypti. Biting deterrence of seeds essential oil with biting deterrence index value of 0.89 was similar to N,N-diethyl-3-methylbenzamide (DEET). All the other oils were active above the solvent control but the activity was significantly lower than DEET. Based on GC-MS analysis, three pure compounds that were only present in the essential oil of seed were further investigated to identify the compounds responsible for biting deterrent activity. 1-Decanol with PNB value of 0.8 was similar to DEET (PNB = 0.8), whereas 1-octanol with PNB value of 0.64 showed biting deterrence lower than 1-decanol and DEET. The activity of 1-heptanol with PNB value of 0.36 was similar to the negative control. Since 1-decanol, which was 3.3% of the seed essential oil, showed biting deterrence similar to DEET as a pure compound, this compound might be responsible for the activity of this oil. In in vitro A & K bioassay, 1-decanol with MED value of 6.25 showed higher repellency than DEET (MED = 12.5). Essential oils of immature and mature fruit showed high toxicity whereas leaf, flower, and seeds essential oils gave only 20%, 0%, and 50% mortality, respectively, at the highest dose of 125 ppm. 1-Decanol with LC50 of 4.8 ppm was the most toxic compound. Full article
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Review

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30 pages, 2664 KiB  
Review
Approaches toward the Separation, Modification, Identification and Scale up Purification of Tetracyclic Diterpene Glycosides from Stevia rebaudiana (Bertoni) Bertoni
by Wilmer H. Perera and James D. McChesney
Molecules 2021, 26(7), 1915; https://doi.org/10.3390/molecules26071915 - 29 Mar 2021
Cited by 6 | Viewed by 3250
Abstract
Stevia rebaudiana (Bertoni) Bertoni is a plant species native to Brazil and Paraguay well-known by the sweet taste of their leaves. Since the recognition of rebaudioside A and other steviol glycosides as generally recognized as safe by the United States Food and Drug [...] Read more.
Stevia rebaudiana (Bertoni) Bertoni is a plant species native to Brazil and Paraguay well-known by the sweet taste of their leaves. Since the recognition of rebaudioside A and other steviol glycosides as generally recognized as safe by the United States Food and Drug Administration in 2008 and grant of marketing approval by the European Union in 2011, the species has been widely cultivated and studied in several countries. Several efforts have been dedicated to the isolation and structure elucidation of minor components searching for novel non-caloric sugar substitutes with improved organoleptic properties. The present review provides an overview of the main chemical approaches found in the literature for identification and structural differentiation of diterpene glycosides from Stevia rebaudiana: High-performance Thin-Layer Chromatography, High-Performance Liquid Chromatography, Electrospray Ionization Mass Spectrometry and Nuclear Magnetic Resonance Spectroscopy. Modification of diterpene glycosides by chemical and enzymatic reactions together with some strategies to scale up of the purification process saving costs are also discussed. A list of natural diterpene glycosides, some examples of chemically modified and of enzymatically modified diterpene glycosides reported from 1931 to February 2021 were compiled using the scientific databases Google Scholar, ScienceDirect and PubMed. Full article
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13 pages, 747 KiB  
Review
Using Micropropagation to Develop Medicinal Plants into Crops
by Rita M. Moraes, Antonio Luiz Cerdeira and Miriam V. Lourenço
Molecules 2021, 26(6), 1752; https://doi.org/10.3390/molecules26061752 - 21 Mar 2021
Cited by 25 | Viewed by 4708
Abstract
Medicinal plants are still the major source of therapies for several illnesses and only part of the herbal products originates from cultivated biomass. Wild harvests represent the major supply for therapies, and such practices threaten species diversity as well as the quality and [...] Read more.
Medicinal plants are still the major source of therapies for several illnesses and only part of the herbal products originates from cultivated biomass. Wild harvests represent the major supply for therapies, and such practices threaten species diversity as well as the quality and safety of the final products. This work intends to show the relevance of developing medicinal plants into crops and the use of micropropagation as technique to mass produce high-demand biomass, thus solving the supply issues of therapeutic natural substances. Herein, the review includes examples of in vitro procedures and their role in the crop development of pharmaceuticals, phytomedicinals, and functional foods. Additionally, it describes the production of high-yielding genotypes, uniform clones from highly heterozygous plants, and the identification of elite phenotypes using bioassays as a selection tool. Finally, we explore the significance of micropropagation techniques for the following: a) pharmaceutical crops for production of small therapeutic molecules (STM), b) phytomedicinal crops for production of standardized therapeutic natural products, and c) the micropropagation of plants for the production of large therapeutic molecules (LTM) including fructooligosaccharides classified as prebiotic and functional food crops. Full article
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27 pages, 1355 KiB  
Review
Ethiopian Medicinal Plants Traditionally Used for the Treatment of Cancer, Part 2: A Review on Cytotoxic, Antiproliferative, and Antitumor Phytochemicals, and Future Perspective
by Solomon Tesfaye, Kaleab Asres, Ermias Lulekal, Yonatan Alebachew, Eyael Tewelde, Mallika Kumarihamy and Ilias Muhammad
Molecules 2020, 25(17), 4032; https://doi.org/10.3390/molecules25174032 - 03 Sep 2020
Cited by 11 | Viewed by 4980
Abstract
This review provides an overview on the active phytochemical constituents of medicinal plants that are traditionally used to manage cancer in Ethiopia. A total of 119 articles published between 1968 and 2020 have been reviewed, using scientific search engines such as ScienceDirect, PubMed, [...] Read more.
This review provides an overview on the active phytochemical constituents of medicinal plants that are traditionally used to manage cancer in Ethiopia. A total of 119 articles published between 1968 and 2020 have been reviewed, using scientific search engines such as ScienceDirect, PubMed, and Google Scholar. Twenty-seven medicinal plant species that belong to eighteen families are documented along with their botanical sources, potential active constituents, and in vitro and in vivo activities against various cancer cells. The review is compiled and discusses the potential anticancer, antiproliferative, and cytotoxic agents based on the types of secondary metabolites, such as terpenoids, phenolic compounds, alkaloids, steroids, and lignans. Among the anticancer secondary metabolites reported in this review, only few have been isolated from plants that are originated and collected in Ethiopia, and the majority of compounds are reported from plants belonging to different areas of the world. Thus, based on the available bioactivity reports, extensive and more elaborate ethnopharmacology-based bioassay-guided studies have to be conducted on selected traditionally claimed Ethiopian anticancer plants, which inherited from a unique and diverse landscape, with the aim of opening a way forward to conduct anticancer drug discovery program. Full article
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