Next Issue
Previous Issue

E-Mail Alert

Add your e-mail address to receive forthcoming issues of this journal:

Journal Browser

Journal Browser

Table of Contents

Molecules, Volume 20, Issue 10 (October 2015), Pages 17684-19646

  • Issues are regarded as officially published after their release is announced to the table of contents alert mailing list.
  • You may sign up for e-mail alerts to receive table of contents of newly released issues.
  • PDF is the official format for papers published in both, html and pdf forms. To view the papers in pdf format, click on the "PDF Full-text" link, and use the free Adobe Readerexternal link to open them.
View options order results:
result details:
Displaying articles 1-108
Export citation of selected articles as:
Open AccessReview Supramolecular Complexation of Carbohydrates for the Bioavailability Enhancement of Poorly Soluble Drugs
Molecules 2015, 20(10), 19620-19646; https://doi.org/10.3390/molecules201019620
Received: 15 September 2015 / Revised: 16 October 2015 / Accepted: 22 October 2015 / Published: 27 October 2015
Cited by 17 | PDF Full-text (1158 KB) | HTML Full-text | XML Full-text
Abstract
In this review, a comprehensive overview of advances in the supramolecular complexes of carbohydrates and poorly soluble drugs is presented. Through the complexation process, poorly soluble drugs could be efficiently delivered to their desired destinations. Carbohydrates, the most abundant biomolecules, have diverse physicochemical
[...] Read more.
In this review, a comprehensive overview of advances in the supramolecular complexes of carbohydrates and poorly soluble drugs is presented. Through the complexation process, poorly soluble drugs could be efficiently delivered to their desired destinations. Carbohydrates, the most abundant biomolecules, have diverse physicochemical properties owing to their inherent three-dimensional structures, hydrogen bonding, and molecular recognition abilities. In this regard, oligosaccharides and their derivatives have been utilized for the bioavailability enhancement of hydrophobic drugs via increasing the solubility or stability. By extension, polysaccharides and their derivatives can form self-assembled architectures with poorly soluble drugs and have shown increased bioavailability in terms of the sustained or controlled drug release. These supramolecular systems using carbohydrate will be developed consistently in the field of pharmaceutical and medical application. Full article
(This article belongs to the Section Medicinal Chemistry)
Figures

Figure 1

Open AccessArticle A Simple, Effective, Green Method for the Regioselective 3-Acylation of Unprotected Indoles
Molecules 2015, 20(10), 19605-19619; https://doi.org/10.3390/molecules201019605
Received: 5 October 2015 / Revised: 22 October 2015 / Accepted: 22 October 2015 / Published: 27 October 2015
Cited by 7 | PDF Full-text (873 KB) | HTML Full-text | XML Full-text
Abstract
A fast and green method is developed for regioselective acylation of indoles in the 3-position without the need for protection of the NH position. The method is based on Friedel-Crafts acylation using acid anhydrides. The method has been optimized, and Y(OTf)3 in
[...] Read more.
A fast and green method is developed for regioselective acylation of indoles in the 3-position without the need for protection of the NH position. The method is based on Friedel-Crafts acylation using acid anhydrides. The method has been optimized, and Y(OTf)3 in catalytic amounts is found to be the best catalyst together with the commercially available ionic liquid [BMI]BF4 (1-butyl-3-methylimidazolium tetrafluoro-borate) as solvent. The reaction is completed in a very short time using monomode microwave irradiation. The catalyst can be reused up to four times without significant loss of activity. A range of substituted indoles are investigated as substrates, and thirteen new compounds have been synthesized. Full article
(This article belongs to the Special Issue Ionic Liquids in Organic Synthesis)
Figures

Figure 1

Open AccessArticle Elevated Expression and Pro-Inflammatory Activity of IL-36 in Patients with Systemic Lupus Erythematosus
Molecules 2015, 20(10), 19588-19604; https://doi.org/10.3390/molecules201019588
Received: 21 September 2015 / Revised: 17 October 2015 / Accepted: 21 October 2015 / Published: 27 October 2015
Cited by 9 | PDF Full-text (3707 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
We investigated the expression and proinflammatory activity of interleukin (IL)-36 in patients with systemic lupus erythematosus (SLE). The expression level of IL-36, its putative receptors and the frequency of CD19+CD24highCD27+ regulatory B (Breg) lymphocytes of peripheral blood from
[...] Read more.
We investigated the expression and proinflammatory activity of interleukin (IL)-36 in patients with systemic lupus erythematosus (SLE). The expression level of IL-36, its putative receptors and the frequency of CD19+CD24highCD27+ regulatory B (Breg) lymphocytes of peripheral blood from 43 SLE patients and 16 normal control (NC) subjects were studied using ELISA and flow cytometry. Plasma cytokines/chemokines and ex vivo productions of cytokine/chemokine from peripheral blood mononuclear cells (PBMC) stimulated with recombinant IL-36 were determined by Luminex multiplex assay. Plasma concentrations of IL-36α, IL-36γ and the proportions of circulating IL-36R-positive CD19+ B lymphocytes in total B lymphocytes and PBMC were significantly increased in active SLE patients compared with NC (all p < 0.05). Plasma IL-36α and IL-36γ correlated positively with SLE disease activity and elevated plasma IL-10 concentration (all p < 0.05). The frequencies of circulating Breg lymphocytes in total B lymphocytes and PBMC were significantly decreased in both inactive and active SLE patients compared with NC (all p < 0.01). The frequency of Breg lymphocytes in total B lymphocytes correlated negatively with the proportion of IL-36R-positive B lymphocytes (p < 0.05). IL-36α exerted substantial proinflammatory effect in PBMC from SLE patients by inducing the production of IL-6 and CXCL8. Upon stimulation with IL-36α and IL-36γ, ex vivo productions of IL-6 and CXCL8 were significantly increased in SLE patients compared with NC (all p < 0.05). This cross-sectional study demonstrated that over expression of circulating IL-36α may exert a proinflammatory effect as observed in human SLE. Full article
(This article belongs to the Section Medicinal Chemistry)
Figures

Figure 1

Open AccessArticle Multivariate Quantification of the Solid State Phase Composition of Co-Amorphous Naproxen-Indomethacin
Molecules 2015, 20(10), 19571-19587; https://doi.org/10.3390/molecules201019571
Received: 25 September 2015 / Revised: 19 October 2015 / Accepted: 21 October 2015 / Published: 27 October 2015
Cited by 4 | PDF Full-text (2280 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
To benefit from the optimized dissolution properties of active pharmaceutical ingredients in their amorphous forms, co-amorphisation as a viable tool to stabilize these amorphous phases is of both academic and industrial interest. Reports dealing with the physical stability and recrystallization behavior of co-amorphous
[...] Read more.
To benefit from the optimized dissolution properties of active pharmaceutical ingredients in their amorphous forms, co-amorphisation as a viable tool to stabilize these amorphous phases is of both academic and industrial interest. Reports dealing with the physical stability and recrystallization behavior of co-amorphous systems are however limited to qualitative evaluations based on the corresponding X-ray powder diffractograms. Therefore, the objective of the study was to develop a quantification model based on X-ray powder diffractometry (XRPD), followed by a multivariate partial least squares regression approach that enables the simultaneous determination of up to four solid state fractions: crystalline naproxen, γ-indomethacin, α-indomethacin as well as co-amorphous naproxen-indomethacin. For this purpose, a calibration set that covers the whole range of possible combinations of the four components was prepared and analyzed by XRPD. In order to test the model performances, leave-one-out cross validation was performed and revealed root mean square errors of validation between 3.11% and 3.45% for the crystalline molar fractions and 5.57% for the co-amorphous molar fraction. In summary, even four solid state phases, involving one co-amorphous phase, can be quantified with this XRPD data-based approach. Full article
(This article belongs to the collection Poorly Soluble Drugs)
Figures

Figure 1

Open AccessReview Starch Modification by Organic Acids and Their Derivatives: A Review
Molecules 2015, 20(10), 19554-19570; https://doi.org/10.3390/molecules201019554
Received: 23 August 2015 / Revised: 14 October 2015 / Accepted: 15 October 2015 / Published: 27 October 2015
Cited by 13 | PDF Full-text (936 KB) | HTML Full-text | XML Full-text
Abstract
Starch has been an inexhaustible subject of research for many decades. It is an inexpensive, readily-available material with extensive application in the food and processing industry. Researchers are continually trying to improve its properties by different modification procedures and expand its application. What
[...] Read more.
Starch has been an inexhaustible subject of research for many decades. It is an inexpensive, readily-available material with extensive application in the food and processing industry. Researchers are continually trying to improve its properties by different modification procedures and expand its application. What is mostly applied in this view are their chemical modifications, among which organic acids have recently drawn the greatest attention, particularly with respect to the application of starch in the food industry. Namely, organic acids naturally occur in many edible plants and many of them are generally recognized as safe (GRAS), which make them ideal modification agents for starch intended for the food industry. The aim of this review is to give a short literature overview of the progress made in the research of starch esterification, etherification, cross-linking, and dual modification with organic acids and their derivatives. Full article
(This article belongs to the Section Natural Products Chemistry)
Figures

Figure 1

Open AccessArticle Unique Reactivity of Transition Metal Atoms Embedded in Graphene to CO, NO, O2 and O Adsorption: A First-Principles Investigation
Molecules 2015, 20(10), 19540-19553; https://doi.org/10.3390/molecules201019540
Received: 18 September 2015 / Revised: 8 October 2015 / Accepted: 16 October 2015 / Published: 27 October 2015
Cited by 4 | PDF Full-text (2287 KB) | HTML Full-text | XML Full-text
Abstract
Taking the adsorption of CO, NO, O2 and O as probes, we investigated the electronic structure of transition metal atoms (TM, TM = Fe, Co, Ni, Cu and Zn) embedded in graphene by first-principles-based calculations. We showed that these TM atoms can
[...] Read more.
Taking the adsorption of CO, NO, O2 and O as probes, we investigated the electronic structure of transition metal atoms (TM, TM = Fe, Co, Ni, Cu and Zn) embedded in graphene by first-principles-based calculations. We showed that these TM atoms can be effectively stabilized on monovacancy defects on graphene by forming plausible interactions with the C atoms associated with dangling bonds. These interactions not only give rise to high energy barriers for the diffusion and aggregation of the embedded TM atoms to withstand the interference of reaction environments, but also shift the energy levels of TM-d states and regulate the reactivity of the embedded TM atoms. The adsorption of CO, NO, O2 and O correlates well with the weight averaged energy level of TM-d states, showing the crucial role of interfacial TM-C interactions on manipulating the reactivity of embedded TM atoms. These findings pave the way for the developments of effective monodispersed atomic TM composites with high stability and desired performance for gas sensing and catalytic applications. Full article
(This article belongs to the Section Medicinal Chemistry)
Figures

Figure 1

Open AccessArticle Fluorescence and Docking Studies of the Interaction between Human Serum Albumin and Pheophytin
Molecules 2015, 20(10), 19526-19539; https://doi.org/10.3390/molecules201019526
Received: 28 September 2015 / Revised: 16 October 2015 / Accepted: 20 October 2015 / Published: 27 October 2015
Cited by 18 | PDF Full-text (1196 KB) | HTML Full-text | XML Full-text
Abstract
In the North of Brazil (Pará and Amazonas states) the leaves of the plant Talinum triangulare (popular: cariru) replace spinach as food. From a phytochemical point of view, they are rich in compounds of the group of pheophytins. These substances, related to
[...] Read more.
In the North of Brazil (Pará and Amazonas states) the leaves of the plant Talinum triangulare (popular: cariru) replace spinach as food. From a phytochemical point of view, they are rich in compounds of the group of pheophytins. These substances, related to chlorophyll, have photophysical properties that give them potential application in photodynamic therapy. Human serum albumin (HSA) is one of the main endogenous vehicles for biodistribution of molecules by blood plasma. Association constants and thermodynamic parameters for the interaction of HSA with pheophytin from Talinum triangulare were studied by UV-Vis absorption, fluorescence techniques, and molecular modeling (docking). Fluorescence quenching of the HSA’s internal fluorophore (tryptophan) at temperatures 296 K, 303 K, and 310 K, resulted in values for the association constants of the order of 104 L∙mol−1, indicating a moderate interaction between the compound and the albumin. The negative values of ΔG° indicate a spontaneous process; ΔH° = 15.5 kJ∙mol−1 indicates an endothermic process of association and ΔS° = 0.145 kJ∙mol−1∙K−1 shows that the interaction between HSA and pheophytin occurs mainly by hydrophobic factors. The observed Trp fluorescence quenching is static: there is initial non-fluorescent association, in the ground state, HSA:Pheophytin. Possible solution obtained by a molecular docking study suggests that pheophytin is able to interact with HSA by means of hydrogen bonds with three lysine and one arginine residues, whereas the phytyl group is inserted in a hydrophobic pocket, close to Trp-214. Full article
(This article belongs to the Section Photochemistry)
Figures

Figure 1

Open AccessReview Antioxidants of Edible Mushrooms
Molecules 2015, 20(10), 19489-19525; https://doi.org/10.3390/molecules201019489
Received: 4 September 2015 / Revised: 19 October 2015 / Accepted: 21 October 2015 / Published: 27 October 2015
Cited by 30 | PDF Full-text (1537 KB) | HTML Full-text | XML Full-text
Abstract
Oxidative stress caused by an imbalanced metabolism and an excess of reactive oxygen species (ROS) lead to a range of health disorders in humans. Our endogenous antioxidant defense mechanisms and our dietary intake of antioxidants potentially regulate our oxidative homeostasis. Numerous synthetic antioxidants
[...] Read more.
Oxidative stress caused by an imbalanced metabolism and an excess of reactive oxygen species (ROS) lead to a range of health disorders in humans. Our endogenous antioxidant defense mechanisms and our dietary intake of antioxidants potentially regulate our oxidative homeostasis. Numerous synthetic antioxidants can effectively improve defense mechanisms, but because of their adverse toxic effects under certain conditions, preference is given to natural compounds. Consequently, the requirements for natural, alternative sources of antioxidant foods identified in edible mushrooms, as well as the mechanistic action involved in their antioxidant properties, have increased rapidly. Chemical composition and antioxidant potential of mushrooms have been intensively studied. Edible mushrooms might be used directly in enhancement of antioxidant defenses through dietary supplementation to reduce the level of oxidative stress. Wild or cultivated, they have been related to significant antioxidant properties due to their bioactive compounds, such as polyphenols, polysaccharides, vitamins, carotenoids and minerals. Antioxidant and health benefits, observed in edible mushrooms, seem an additional reason for their traditional use as a popular delicacy food. This review discusses the consumption of edible mushrooms as a powerful instrument in maintaining health, longevity and life quality. Full article
(This article belongs to the Special Issue Antioxidants—A Risk-Benefit Analysis for Health)
Figures

Figure 1

Open AccessArticle Comparative Study of the Optical and Textural Properties of Tetrapyrrole Macrocycles Trapped Within ZrO2, TiO2, and SiO2 Translucent Xerogels
Molecules 2015, 20(10), 19463-19488; https://doi.org/10.3390/molecules201019463
Received: 1 August 2015 / Revised: 17 September 2015 / Accepted: 15 October 2015 / Published: 23 October 2015
Cited by 5 | PDF Full-text (10701 KB) | HTML Full-text | XML Full-text
Abstract
The entrapping of physicochemical active molecules inside mesoporous networks is an appealing field of research due to the myriad of potential applications in optics, photocatalysis, chemical sensing, and medicine. One of the most important reasons for this success is the possibility of optimizing
[...] Read more.
The entrapping of physicochemical active molecules inside mesoporous networks is an appealing field of research due to the myriad of potential applications in optics, photocatalysis, chemical sensing, and medicine. One of the most important reasons for this success is the possibility of optimizing the properties that a free active species displays in solution but now trapped inside a solid substrate. Additionally it is possible to modulate the textural characteristics of substrates, such as pore size, specific surface area, polarity and chemical affinity of the surface, toward the physical or chemical adhesion of a variety of adsorbates. In the present document, two kinds of non-silicon metal alkoxides, Zr and Ti, are employed to prepare xerogels containing entrapped tetrapyrrolic species that could be inserted beforehand in analogue silica systems. The main goal is to develop efficient methods for trapping or binding tetrapyrrole macrocycles inside TiO2 and ZrO2 xerogels, while comparing the properties of these systems against those of the SiO2 analogues. Once the optimal synthesis conditions for obtaining translucent monolithic xerogels of ZrO2 and TiO2 networks were determined, it was confirmed that these substrates allowed the entrapment, in monomeric form, of macrocycles that commonly appear as aggregates within the SiO2 network. From these experiments, it could be determined that the average pore diameters, specific surface areas, and water sorption capacities depicted by each one of these substrates, are a consequence of their own nature combined with the particular structure of the entrapped tetrapyrrole macrocycle. Furthermore, the establishment of covalent bonds between the intruding species and the pore walls leads to the obtainment of very similar pore sizes in the three different metal oxide (Ti, Zr, and Si) substrates as a consequence of the templating effect of the encapsulated species. Full article
(This article belongs to the Special Issue Tetrapyrroles, Porphyrins and Phthalocyanines)
Figures

Figure 1

Open AccessCommunication Selective Halogen-Lithium Exchange of 1,2-Dihaloarenes for Successive [2+4] Cycloadditions of Arynes and Isobenzofurans
Molecules 2015, 20(10), 19449-19462; https://doi.org/10.3390/molecules201019449
Received: 1 October 2015 / Revised: 15 October 2015 / Accepted: 20 October 2015 / Published: 23 October 2015
Cited by 3 | PDF Full-text (795 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Successive [2+4] cycloadditions of arynes and isobenzofurans by site-selective halogen-lithium exchange of 1,2-dihaloarenes were developed, allowing the rapid construction of polycyclic compounds which serve as a useful synthetic intermediates for the preparation of various polyacene derivatives. Full article
(This article belongs to the Special Issue Development and Application of Aryne Chemistry in Organic Synthesis)
Figures

Figure 1

Open AccessReview The Multiple Roles of Microrna-223 in Regulating Bone Metabolism
Molecules 2015, 20(10), 19433-19448; https://doi.org/10.3390/molecules201019433
Received: 14 September 2015 / Revised: 13 October 2015 / Accepted: 20 October 2015 / Published: 23 October 2015
Cited by 11 | PDF Full-text (759 KB) | HTML Full-text | XML Full-text
Abstract
Bone metabolism is a lifelong process for maintaining skeletal system homeostasis, which is regulated by bone-resorbing osteoclasts and bone-forming osteoblasts. Aberrant differentiation of osteoclasts and osteoblasts leads to imbalanced bone metabolism, resulting in ossification and osteolysis diseases. MicroRNAs (miRNAs) are pivotal factors in
[...] Read more.
Bone metabolism is a lifelong process for maintaining skeletal system homeostasis, which is regulated by bone-resorbing osteoclasts and bone-forming osteoblasts. Aberrant differentiation of osteoclasts and osteoblasts leads to imbalanced bone metabolism, resulting in ossification and osteolysis diseases. MicroRNAs (miRNAs) are pivotal factors in regulating bone metabolism via post-transcriptional inhibition of target genes. Recent studies have revealed that miR-223 exerts multiple effects on bone metabolism, especially in the processes of osteoclast and osteoblasts differentiation. In this review, we highlight the roles of miR-223 during the processes of osteoclast and osteoblast differentiation, as well as the potential clinical applications of miR-223 in bone metabolism disorders. Full article
(This article belongs to the Section Molecular Diversity)
Figures

Figure 1

Open AccessReview Effects of Flavonoids from Food and Dietary Supplements on Glial and Glioblastoma Multiforme Cells
Molecules 2015, 20(10), 19406-19432; https://doi.org/10.3390/molecules201019406
Received: 31 July 2015 / Revised: 21 September 2015 / Accepted: 14 October 2015 / Published: 23 October 2015
Cited by 12 | PDF Full-text (892 KB) | HTML Full-text | XML Full-text
Abstract
Quercetin, catechins and proanthocyanidins are flavonoids that are prominently featured in foodstuffs and dietary supplements, and may possess anti-carcinogenic activity. Glioblastoma multiforme is the most dangerous form of glioma, a malignancy of the brain connective tissue. This review assesses molecular structures of these
[...] Read more.
Quercetin, catechins and proanthocyanidins are flavonoids that are prominently featured in foodstuffs and dietary supplements, and may possess anti-carcinogenic activity. Glioblastoma multiforme is the most dangerous form of glioma, a malignancy of the brain connective tissue. This review assesses molecular structures of these flavonoids, their importance as components of diet and dietary supplements, their bioavailability and ability to cross the blood-brain barrier, their reported beneficial health effects, and their effects on non-malignant glial as well as glioblastoma tumor cells. The reviewed flavonoids appear to protect glial cells via reduction of oxidative stress, while some also attenuate glutamate-induced excitotoxicity and reduce neuroinflammation. Most of the reviewed flavonoids inhibit proliferation of glioblastoma cells and induce their death. Moreover, some of them inhibit pro-oncogene signaling pathways and intensify the effect of conventional anti-cancer therapies. However, most of these anti-glioblastoma effects have only been observed in vitro or in animal models. Due to limited ability of the reviewed flavonoids to access the brain, their normal dietary intake is likely insufficient to produce significant anti-cancer effects in this organ, and supplementation is needed. Full article
Figures

Figure 1

Open AccessArticle A Practical Route for the Preparation of 1,4,7-Triazacyclononanyl Diacetates with a Hydroxypyridinonate Pendant Arm
Molecules 2015, 20(10), 19393-19405; https://doi.org/10.3390/molecules201019393
Received: 2 September 2015 / Revised: 16 October 2015 / Accepted: 16 October 2015 / Published: 23 October 2015
Cited by 6 | PDF Full-text (781 KB) | HTML Full-text | XML Full-text
Abstract
The preparation of triazamacrocyclic hydroxypyridinonate (HOPO-TACN) derivatives as potential chelators for metals in biomedical applications was reported. The synthesis is based on a convergent synthetic approach, in which the key intermediate di-tert-butyl-2,2′-(1,4,7-triazonane-1,4-diyl) diacetate was coupled with a hydroxypyridinonate pendant arm. The
[...] Read more.
The preparation of triazamacrocyclic hydroxypyridinonate (HOPO-TACN) derivatives as potential chelators for metals in biomedical applications was reported. The synthesis is based on a convergent synthetic approach, in which the key intermediate di-tert-butyl-2,2′-(1,4,7-triazonane-1,4-diyl) diacetate was coupled with a hydroxypyridinonate pendant arm. The method is suitable for rapid syntheses of metal chelator HOPO-TACNs of biomedical interest. Full article
(This article belongs to the Section Organic Chemistry)
Figures

Figure 1

Open AccessArticle Purification and Partial Characterization of β-Glucosidase in Chayote (Sechium edule)
Molecules 2015, 20(10), 19372-19392; https://doi.org/10.3390/molecules201019372
Received: 17 August 2015 / Revised: 7 October 2015 / Accepted: 10 October 2015 / Published: 23 October 2015
Cited by 2 | PDF Full-text (1250 KB) | HTML Full-text | XML Full-text
Abstract
β-Glucosidase (EC 3.2.1.21) is a prominent member of the GH1 family of glycoside hydrolases. The properties of this β-glucosidase appear to include resistance to temperature, urea, and iodoacetamide, and it is activated by 2-ME, similar to other members. β-Glucosidase from chayote (Sechium
[...] Read more.
β-Glucosidase (EC 3.2.1.21) is a prominent member of the GH1 family of glycoside hydrolases. The properties of this β-glucosidase appear to include resistance to temperature, urea, and iodoacetamide, and it is activated by 2-ME, similar to other members. β-Glucosidase from chayote (Sechium edule) was purified by ionic-interchange chromatography and molecular exclusion chromatography. Peptides detected by LC-ESI-MS/MS were compared with other β-glucosidases using the BLAST program. This enzyme is a 116 kDa protein composed of two sub-units of 58 kDa and shows homology with Cucumis sativus β-glucosidase (NCBI reference sequence XP_004154617.1), in which seven peptides were found with relative masses ranging from 874.3643 to 1587.8297. The stability of β-glucosidase depends on an initial concentration of 0.2 mg/mL of protein at pH 5.0 which decreases by 33% in a period of 30 h, and then stabilizes and is active for the next 5 days (pH 4.0 gives similar results). One hundred μg/mL β-D-glucose inhibited β-glucosidase activity by more than 50%. The enzyme had a Km of 4.88 mM with p-NPG and a Kcat of 10,000 min−1. The optimal conditions for the enzyme require a pH of 4.0 and a temperature of 50 °C. Full article
(This article belongs to the Section Natural Products Chemistry)
Figures

Figure 1

Open AccessArticle Design, Synthesis, Activity and Docking Study of Sorafenib Analogs Bearing Sulfonylurea Unit
Molecules 2015, 20(10), 19361-19371; https://doi.org/10.3390/molecules201019361
Received: 10 August 2015 / Revised: 21 September 2015 / Accepted: 21 September 2015 / Published: 23 October 2015
Cited by 17 | PDF Full-text (296 KB) | HTML Full-text | XML Full-text
Abstract
Two series of novel sorafenib analogs containing a sulfonylurea unit were synthesized and their chemical structures were confirmed by 1H-NMR, 13C-NMR, MS spectrum and elemental analysis. The synthesized compounds were evaluated for the cytotoxicity against A549, Hela, MCF-7, and PC-3
[...] Read more.
Two series of novel sorafenib analogs containing a sulfonylurea unit were synthesized and their chemical structures were confirmed by 1H-NMR, 13C-NMR, MS spectrum and elemental analysis. The synthesized compounds were evaluated for the cytotoxicity against A549, Hela, MCF-7, and PC-3 cancer cell lines. Some of the compounds showed moderate cytotoxic activity, especially compounds 1-(2,4-difluorophenylsulfonyl)-3-(4-(2-(methylcarbamoyl)pyridin-4-yloxy)phenyl)urea (6c) and 1-(4-bromophenylsulfonyl)-3-(4-(2-(methylcarbamoyl)pyridin-4-yloxy)phenyl)urea (6f) with the IC50 values against four cancer cell lines ranging from 16.54 ± 1.22 to 63.92 ± 1.81 μM, respectively. Inhibitory rates against vascular endothelial growth factor receptor-2 (VEGFR2/KDR) kinase at 10 μM of target compounds were further carried out in this paper in order to investigate the target of these compounds. Structure-activity relationships (SARs) and docking studies indicated that the sulfonylurea unit was important to these kinds of compounds. None of the substitutions in the phenoxy group and small halogen atoms such as 2,4-difluoro substitution of the aryl group contributed to the activity. The results suggested that sulfonylurea sorafenib analogs are worthy of further study. Full article
Figures

Figure 1

Back to Top