The solid-liquid equilibrium of benzoic acid derivatives in 1-octanol was first determined in this article. Using a laser monitoring observation technique, the solubility data of o-amino-benzoic acid, p-amino-benzoic ...The solid-liquid equilibrium of benzoic acid derivatives in 1-octanol was first determined in this article. Using a laser monitoring observation technique, the solubility data of o-amino-benzoic acid, p-amino-benzoic acid,o-chloro-benzoic acid, and m-nitro-benzoic acid in 1-octanol were measured by the polythermal method in the temperature range of 20-50℃. The experimental data were regressed with the. Wilson equation and the λH equation. The experimental results showed that the solubility of the four chemicals in 1-octanol increased significantly with temperature. The results indicate that the molecular structure and interactions affect the solubility significantly.The solubility order of the benzoic acid derivatives is as follows： m-nitro-benzoic acid〉o-chloro-benzoic acid〉 o-amino-benzoic acid〉p-amino-benzoic acid. Both the Wilson equation and λH equation are in good agreement with the experimental data.展开更多
actoxy-19-nor-progesterone was synthesized by a new efficient stereoselective asymmertric pathway from 19-nor-androst-4-en-3,17-dione in 5-steps reactions with overall yield 63.3%. Consequently, a strategy was used to...actoxy-19-nor-progesterone was synthesized by a new efficient stereoselective asymmertric pathway from 19-nor-androst-4-en-3,17-dione in 5-steps reactions with overall yield 63.3%. Consequently, a strategy was used to produce of 17-α-hydroxyl compound stereoselectively by addition 17-keto steroid with hydrogen cyanide, at the same time, the conditions of this asymmertric reaction were optimized. The titled compound and the intermediate were fully characterized by 1H, one dimension and two dimension 13C-nuclear magnetic resonance, and infrared spectrum. The results show that the rate of 17-α-hydroxyl compound isomeride is sensitively affected by the solution system and the best volume ratio of CH3OH to H2O is 36%. After the carbonyl and hydroxyl groups were protected by ethylenediol and vinyl butyl ether respectively, organometallic addition to CN group with CH3Li, androstance compound was converted to pregnane compound. After removing the protective groups by a mild hydrolytic procedure with high yield, the titled compound was obtained by esterified the above intermidiate. The new pathway gives a good purity of 98% as determined by high performance liquid chromatography.展开更多
Inhibition of 11βHSD1 （11-beta-hydroxysteroid dehydrogenase 1） is a promising strategy in drug treatment of diabetes. Several 11βHSDI inhibitors have been proposed; however, their selectivity to 11βHSD1 over its ...Inhibition of 11βHSD1 （11-beta-hydroxysteroid dehydrogenase 1） is a promising strategy in drug treatment of diabetes. Several 11βHSDI inhibitors have been proposed; however, their selectivity to 11βHSD1 over its isozyme 11βHSD2 （11-beta-hydroxysteroid dehydrogenase 2） has not been fully reported. The authors sought to provide a short list of top potent and selective compounds along with their detailed binding modes and pharmacophore models, Molecular docking was used for initial screening of a set of 23 potent inhibitors reported by previous experimental studies. After that, selected promising entries were reassessed by molecular dynamics simulations, followed by hydrogen bond analysis. Pharmacophore models of all drug candidates and binding modes of some selected drugs were analyzed. Among the 23 compounds, only four inhibitors were identified as potent and selective drug candidates. Binding energies, 3D pharmacophores and binding modes of the four compounds with 11βHSDI are also discussed in detail in this study.展开更多
Anti-HIV screening with the MT-4/MTT assay on a focused library of structurally diverse natural products has led to the discovery of a group of steroids with potent activities, which include four new ergostane-type st...Anti-HIV screening with the MT-4/MTT assay on a focused library of structurally diverse natural products has led to the discovery of a group of steroids with potent activities, which include four new ergostane-type steroids, named amotsterols A-D （1-4）, together with two known analogs. Among them, the most potent amotsterol D （4） exhibited anti-HIV activity against wild- type and some clinically relevant multidrug resistant HIV-I strains. Subsequent studies on its target identification through a proteomic approach found that compound 4 might target PKM2, a rate limiting enzyme ofglycolysis, in host cells to restrict HIV replication. The docking model of compound 4 to PKM2 showed that the two hydroxyl groups of 4 form hydrogen bonds with the two parallel Y390 in each subunit of PKM2 separately, and the ring C of 4 is sandwiched between the two parallel aromatic rings ofF26. The identified hit compound may have the potential to be further developed as a novel anti-HIVagent. These results demonstrated that an integrated approach, which combines new chemical structures and phenotypic screening with a proteomic approach, could not only identify novel HIV-1 inhibitors, but also elucidate the unknown targets of compound interactions in antiviral drug discovery.展开更多
OBJECTIVE: To assess the phytochemical contents and antioxidant activities of crude extracts from selected Tulbaghia species.METHODS: Standard methods were used for preliminary phytochemical analysis. The total phenol...OBJECTIVE: To assess the phytochemical contents and antioxidant activities of crude extracts from selected Tulbaghia species.METHODS: Standard methods were used for preliminary phytochemical analysis. The total phenolic acid contents of the plant extracts were determined using the Folin-Ciocalteu method, and the total flavonoid contents were determined using the aluminum chloride colorimetric method. 1,1-Diphenyl-2-picrylhydrazyl and 2,2′-Azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) assays were used to evaluate the antioxidant activities.RESULTS: Phytochemical screening showed flavonoids, glycosides, tannins, terpenoids, saponins,and steroids were present in the Tulbaghia species.The total phenolic acid and flavonoid contents varied in the different plant extracts, ranging from4.50 to 11.10 mg of gallic acid equivalents per gram of fresh material and 3.04 to 9.65 mg of quercetin equivalents per gram, respectively. The IC50 values determined for Tulbaghia alliacea and Tulbaghia violacea based on 1,1-diphenyl-2-picrylhydrazyl(0.06 and 0.08 mg/m L, respectively) and 2,2′-Azino-bis(3-ethylbenzthiazoline-6-sulfonic acid)(0.06 and 0.03 mg/m L, respectively) were low and showed they had potential antioxidant activities.CONCLUSION: Our results suggest that individual compounds from Tulbaghia species should be isolated for analysis of their antioxidant activity because some compounds may work best when pure.展开更多
基金Supported by the National Natural Science Foundation of China （No.20676101） and the Natural Science Foundation of Tianjin University of Science ＆ Technology （No.20050207）.
文摘The solid-liquid equilibrium of benzoic acid derivatives in 1-octanol was first determined in this article. Using a laser monitoring observation technique, the solubility data of o-amino-benzoic acid, p-amino-benzoic acid,o-chloro-benzoic acid, and m-nitro-benzoic acid in 1-octanol were measured by the polythermal method in the temperature range of 20-50℃. The experimental data were regressed with the. Wilson equation and the λH equation. The experimental results showed that the solubility of the four chemicals in 1-octanol increased significantly with temperature. The results indicate that the molecular structure and interactions affect the solubility significantly.The solubility order of the benzoic acid derivatives is as follows： m-nitro-benzoic acid〉o-chloro-benzoic acid〉 o-amino-benzoic acid〉p-amino-benzoic acid. Both the Wilson equation and λH equation are in good agreement with the experimental data.
文摘actoxy-19-nor-progesterone was synthesized by a new efficient stereoselective asymmertric pathway from 19-nor-androst-4-en-3,17-dione in 5-steps reactions with overall yield 63.3%. Consequently, a strategy was used to produce of 17-α-hydroxyl compound stereoselectively by addition 17-keto steroid with hydrogen cyanide, at the same time, the conditions of this asymmertric reaction were optimized. The titled compound and the intermediate were fully characterized by 1H, one dimension and two dimension 13C-nuclear magnetic resonance, and infrared spectrum. The results show that the rate of 17-α-hydroxyl compound isomeride is sensitively affected by the solution system and the best volume ratio of CH3OH to H2O is 36%. After the carbonyl and hydroxyl groups were protected by ethylenediol and vinyl butyl ether respectively, organometallic addition to CN group with CH3Li, androstance compound was converted to pregnane compound. After removing the protective groups by a mild hydrolytic procedure with high yield, the titled compound was obtained by esterified the above intermidiate. The new pathway gives a good purity of 98% as determined by high performance liquid chromatography.
文摘Inhibition of 11βHSD1 （11-beta-hydroxysteroid dehydrogenase 1） is a promising strategy in drug treatment of diabetes. Several 11βHSDI inhibitors have been proposed; however, their selectivity to 11βHSD1 over its isozyme 11βHSD2 （11-beta-hydroxysteroid dehydrogenase 2） has not been fully reported. The authors sought to provide a short list of top potent and selective compounds along with their detailed binding modes and pharmacophore models, Molecular docking was used for initial screening of a set of 23 potent inhibitors reported by previous experimental studies. After that, selected promising entries were reassessed by molecular dynamics simulations, followed by hydrogen bond analysis. Pharmacophore models of all drug candidates and binding modes of some selected drugs were analyzed. Among the 23 compounds, only four inhibitors were identified as potent and selective drug candidates. Binding energies, 3D pharmacophores and binding modes of the four compounds with 11βHSDI are also discussed in detail in this study.
基金supported by the National Natural Science Foundation of China (21532007, U1302222)the "Personalized Medicines-Molecular Signature-based Drug Discovery and Development"+1 种基金Strategic Priority Research Program of the Chinese Academy of Sciences (XDA12020321)the Canadian Institutes for Health Research (CIHR)
文摘Anti-HIV screening with the MT-4/MTT assay on a focused library of structurally diverse natural products has led to the discovery of a group of steroids with potent activities, which include four new ergostane-type steroids, named amotsterols A-D （1-4）, together with two known analogs. Among them, the most potent amotsterol D （4） exhibited anti-HIV activity against wild- type and some clinically relevant multidrug resistant HIV-I strains. Subsequent studies on its target identification through a proteomic approach found that compound 4 might target PKM2, a rate limiting enzyme ofglycolysis, in host cells to restrict HIV replication. The docking model of compound 4 to PKM2 showed that the two hydroxyl groups of 4 form hydrogen bonds with the two parallel Y390 in each subunit of PKM2 separately, and the ring C of 4 is sandwiched between the two parallel aromatic rings ofF26. The identified hit compound may have the potential to be further developed as a novel anti-HIVagent. These results demonstrated that an integrated approach, which combines new chemical structures and phenotypic screening with a proteomic approach, could not only identify novel HIV-1 inhibitors, but also elucidate the unknown targets of compound interactions in antiviral drug discovery.
基金Supported by Vaal University of Technology,Private Bag X021,Vanderbijlpark 1900,South Africa
文摘OBJECTIVE: To assess the phytochemical contents and antioxidant activities of crude extracts from selected Tulbaghia species.METHODS: Standard methods were used for preliminary phytochemical analysis. The total phenolic acid contents of the plant extracts were determined using the Folin-Ciocalteu method, and the total flavonoid contents were determined using the aluminum chloride colorimetric method. 1,1-Diphenyl-2-picrylhydrazyl and 2,2′-Azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) assays were used to evaluate the antioxidant activities.RESULTS: Phytochemical screening showed flavonoids, glycosides, tannins, terpenoids, saponins,and steroids were present in the Tulbaghia species.The total phenolic acid and flavonoid contents varied in the different plant extracts, ranging from4.50 to 11.10 mg of gallic acid equivalents per gram of fresh material and 3.04 to 9.65 mg of quercetin equivalents per gram, respectively. The IC50 values determined for Tulbaghia alliacea and Tulbaghia violacea based on 1,1-diphenyl-2-picrylhydrazyl(0.06 and 0.08 mg/m L, respectively) and 2,2′-Azino-bis(3-ethylbenzthiazoline-6-sulfonic acid)(0.06 and 0.03 mg/m L, respectively) were low and showed they had potential antioxidant activities.CONCLUSION: Our results suggest that individual compounds from Tulbaghia species should be isolated for analysis of their antioxidant activity because some compounds may work best when pure.
