The support vector classification （SVC） was employed to make a model for classification of antifungal activities of 1-（1H-1,2,4-triazole-l-yl）-2-（2,4-difluorophenyl）-3-substituted-2-propanols triazole derivative...The support vector classification （SVC） was employed to make a model for classification of antifungal activities of 1-（1H-1,2,4-triazole-l-yl）-2-（2,4-difluorophenyl）-3-substituted-2-propanols triazole derivatives. The compounds with high antifungal activities and those with low antifungal activities were compared on the basis of the following molecular descriptors： net atomic charge on the atom N connecting with R, dipole moment and heat of formation, By using the SVC, a mathematical model was constructed, which can predict the antifungal activities of the triazole derivatives, with an accuracy of 91% on the basis of the leave-one-out cross-validation （LOOCV） test, The results indicate that the performance of the SVC model can exceed that of the principal component analysis （PCA） and K-Nearest Neighbor （KNN） models for this real world data set.展开更多
1, 3, 4-Oxadiazole derivatives(4 a–5 f) were previously synthesized to investigate their anticancer properties.However, studies relating to their antioxidant potential and signal transducer and activator of transcrip...1, 3, 4-Oxadiazole derivatives(4 a–5 f) were previously synthesized to investigate their anticancer properties.However, studies relating to their antioxidant potential and signal transducer and activator of transcription(STAT) inhibition have not been performed. We investigated previously synthesized 1, 3, 4-oxadiazole derivatives(4 a–5 f) for various radical scavenging properties using several in vitro antioxidant assays and also for direct inhibition of STAT3 through molecular docking. The data obtained from various antioxidant assays such as 2, 2,-diphenyl-1-picrylhydrazyl radical(DPPH), nitric oxide, hydrogen peroxide, and superoxide anion radical revealed that among all the derivatives, compound 5 e displayed high antioxidant activities than the standard antioxidant L-ascorbic acid. Additionally, the total reduction assay and antioxidant capacity assay further confirmed the antioxidant potential of compound 5 e. Furthermore, the molecular docking studies performed for all derivatives along with the standard inhibitor STX-0119 showed that binding energy released in direct binding with the SH2 domain of STAT3 was the highest for compound 5 e(-9.91 kcal/mol).Through virtual screening, compound 5 e was found to exhibit optimum competency in inhibiting STAT3 activity. Compound 5 e decreased the activation of STAT3 as observed with Western blot. In brief, compound5 e was identified as a potent antioxidant agent and STAT3 inhibitor and effective agent for cancer treatment.展开更多
Gambogic acid （GA, 1）, the most prominent representative of Garcinia natural products, has been reported to be a promising anti-tumor agent. In order to further explore the structure-activity relationship of GA and ...Gambogic acid （GA, 1）, the most prominent representative of Garcinia natural products, has been reported to be a promising anti-tumor agent. In order to further explore the structure-activity relationship of GA and discover novel GA derivatives as anti-tumor agents, 17 novel C-37 modified derivatives of GA were synthesized and evaluated for their in vitro anti-tumor activities against A549, HCT-116, BGC-823, HepG2 and MCF-7 cancer cell lines. Among them, 11 compounds were found to be more potent than GA against some cancer cell lines. Notably, com- pound 8 was almost 5--10 folds more active than GA against A549 and BGC-823 cell lines with the IC50 values of 0.12 μmol·L^-1 and 0.57 μmol·L^-1, respectively. Chemical modification at C-37 position of GA by introducing of hydrophilic amines could lead to increased activity and improved drug-like properties. These findings will enhance our understanding of the structure-activity relationship （SAR） of GA and lead to the discovery of novel GA derivatives as potential anti-tumor agents.展开更多
基金Project supported by the National Natural Science Foundation of China （Grant Nos.20373040, 20503015）
文摘The support vector classification （SVC） was employed to make a model for classification of antifungal activities of 1-（1H-1,2,4-triazole-l-yl）-2-（2,4-difluorophenyl）-3-substituted-2-propanols triazole derivatives. The compounds with high antifungal activities and those with low antifungal activities were compared on the basis of the following molecular descriptors： net atomic charge on the atom N connecting with R, dipole moment and heat of formation, By using the SVC, a mathematical model was constructed, which can predict the antifungal activities of the triazole derivatives, with an accuracy of 91% on the basis of the leave-one-out cross-validation （LOOCV） test, The results indicate that the performance of the SVC model can exceed that of the principal component analysis （PCA） and K-Nearest Neighbor （KNN） models for this real world data set.
基金supported by UGC (University Grant Commission) (F no.- 43-172/2014 (SR))
文摘1, 3, 4-Oxadiazole derivatives(4 a–5 f) were previously synthesized to investigate their anticancer properties.However, studies relating to their antioxidant potential and signal transducer and activator of transcription(STAT) inhibition have not been performed. We investigated previously synthesized 1, 3, 4-oxadiazole derivatives(4 a–5 f) for various radical scavenging properties using several in vitro antioxidant assays and also for direct inhibition of STAT3 through molecular docking. The data obtained from various antioxidant assays such as 2, 2,-diphenyl-1-picrylhydrazyl radical(DPPH), nitric oxide, hydrogen peroxide, and superoxide anion radical revealed that among all the derivatives, compound 5 e displayed high antioxidant activities than the standard antioxidant L-ascorbic acid. Additionally, the total reduction assay and antioxidant capacity assay further confirmed the antioxidant potential of compound 5 e. Furthermore, the molecular docking studies performed for all derivatives along with the standard inhibitor STX-0119 showed that binding energy released in direct binding with the SH2 domain of STAT3 was the highest for compound 5 e(-9.91 kcal/mol).Through virtual screening, compound 5 e was found to exhibit optimum competency in inhibiting STAT3 activity. Compound 5 e decreased the activation of STAT3 as observed with Western blot. In brief, compound5 e was identified as a potent antioxidant agent and STAT3 inhibitor and effective agent for cancer treatment.
基金Acknowledgement This work was supported by the National Natural Science Foundation of China （Nos. 90713038, 21072231, 30873157） and National Major Science and Technology Project of China （Innovation and Development of New Drugs. Nos. 2008ZX09401-001, 2009ZX09501-003）.
文摘Gambogic acid （GA, 1）, the most prominent representative of Garcinia natural products, has been reported to be a promising anti-tumor agent. In order to further explore the structure-activity relationship of GA and discover novel GA derivatives as anti-tumor agents, 17 novel C-37 modified derivatives of GA were synthesized and evaluated for their in vitro anti-tumor activities against A549, HCT-116, BGC-823, HepG2 and MCF-7 cancer cell lines. Among them, 11 compounds were found to be more potent than GA against some cancer cell lines. Notably, com- pound 8 was almost 5--10 folds more active than GA against A549 and BGC-823 cell lines with the IC50 values of 0.12 μmol·L^-1 and 0.57 μmol·L^-1, respectively. Chemical modification at C-37 position of GA by introducing of hydrophilic amines could lead to increased activity and improved drug-like properties. These findings will enhance our understanding of the structure-activity relationship （SAR） of GA and lead to the discovery of novel GA derivatives as potential anti-tumor agents.
