The Experts below are selected from a list of 4509 Experts worldwide ranked by ideXlab platform
Fan-hao Meng - One of the best experts on this subject based on the ideXlab platform.
-
design synthesis and biological evaluation of n 4 alkoxy 3 cyanophenyl isonicotinamide nicotinamide derivatives as novel xanthine oxidase inhibitors
European Journal of Medicinal Chemistry, 2017Co-Authors: Ting-jian Zhang, Qi Sun, Lin Wang, Yi Zhang, Fan-hao MengAbstract:Abstract A series of N-(4-alkoxy-3-cyanophenyl)isonicotinamide/nicotinamide derivatives was designed, synthesized and evaluated for inhibitory potency in vitro against xanthine oxidase. The isonicotinamide series was considerably more effective than the nicotinamide series. SARs analysis revealed that the isonicotinoyl moiety played a significant role on the inhibition and that a benzyl ether tail (e.g., ortho-cyanobenzoxy) linked to the benzonitrile moiety benefits the inhibitory potency. Among these compounds, 10q (IC50 = 0.3 μM) was identified to be the most potent in this work and was observed to be 28.3-fold more potent than allopurinol but 20-fold less potent than topiroxostat. The Lineweaver-Burk plot showed that 10q acted as a mixed-type inhibitor on xanthine oxidase. Molecular modeling provided a reasonable explanation for the SARs observed in this study.
-
Design, synthesis, and biological evaluation of 5-(4-(pyridin-4-yl)-1H-1,2,3-triazol-1-yl)benzonitrile derivatives as xanthine oxidase inhibitors.
Chemical biology & drug design, 2017Co-Authors: Ting-jian Zhang, Li Songye, Yi Zhang, Fan-hao MengAbstract:A series of 5-(4-(pyridin-4-yl)-1H-1,2,3-triazol-1-yl)benzonitrile derivatives (1a-p) was designed, synthesized, and identified as xanthine oxidase inhibitors with micromolar level potencies. Among them, the most promising compounds 1j and 1k were obtained with IC50 values of 8.1 and 6.7 μm, respectively. The Lineweaver-Burk plot revealed that compound 1k acted as a mixed-type xanthine oxidase inhibitor. SAR analysis revealed that a carbon atom occupying the X3 position is not as effective as a nitrogen atom, and an iso-pentyloxy or a cyclopentyloxy at the 2-position of benzonitrile moiety will benefit the inhibitory potency. The basis of xanthine oxidase inhibition by 1k was rationalized by molecular modeling studies.
-
Discovery and biological evaluation of some (1H-1,2,3-triazol-4-yl)methoxybenzaldehyde derivatives containing an anthraquinone moiety as potent xanthine oxidase inhibitors
Bioorganic and Medicinal Chemistry Letters, 2017Co-Authors: Ting-jian Zhang, Qing Xia Wu, Song-ye Li, Wei-yan Yuan, Su Yang, Qi Sun, Lin Wang, Fan-hao MengAbstract:A series of (1H-1,2,3-triazol-4-yl)methoxybenzaldehyde derivatives containing an anthraquinone moiety were synthesized and identified as novel xanthine oxidase inhibitors. Among them, the most promising compounds 1h and 1k were obtained with IC50values of 0.6 μM and 0.8 μM, respectively, which were more than 10-fold potent compared with allopurinol. The Lineweaver-Burk plot revealed that compound 1h acted as a mixed-type xanthine oxidase inhibitor. SAR analysis showed that the benzaldehyde moiety played a more important role than the anthraquinone moiety for inhibition potency. The basis of significant inhibition of xanthine oxidase by 1h was rationalized by molecular modeling studies.
Ting-jian Zhang - One of the best experts on this subject based on the ideXlab platform.
-
design synthesis and biological evaluation of n 4 alkoxy 3 cyanophenyl isonicotinamide nicotinamide derivatives as novel xanthine oxidase inhibitors
European Journal of Medicinal Chemistry, 2017Co-Authors: Ting-jian Zhang, Qi Sun, Lin Wang, Yi Zhang, Fan-hao MengAbstract:Abstract A series of N-(4-alkoxy-3-cyanophenyl)isonicotinamide/nicotinamide derivatives was designed, synthesized and evaluated for inhibitory potency in vitro against xanthine oxidase. The isonicotinamide series was considerably more effective than the nicotinamide series. SARs analysis revealed that the isonicotinoyl moiety played a significant role on the inhibition and that a benzyl ether tail (e.g., ortho-cyanobenzoxy) linked to the benzonitrile moiety benefits the inhibitory potency. Among these compounds, 10q (IC50 = 0.3 μM) was identified to be the most potent in this work and was observed to be 28.3-fold more potent than allopurinol but 20-fold less potent than topiroxostat. The Lineweaver-Burk plot showed that 10q acted as a mixed-type inhibitor on xanthine oxidase. Molecular modeling provided a reasonable explanation for the SARs observed in this study.
-
Design, synthesis, and biological evaluation of 5-(4-(pyridin-4-yl)-1H-1,2,3-triazol-1-yl)benzonitrile derivatives as xanthine oxidase inhibitors.
Chemical biology & drug design, 2017Co-Authors: Ting-jian Zhang, Li Songye, Yi Zhang, Fan-hao MengAbstract:A series of 5-(4-(pyridin-4-yl)-1H-1,2,3-triazol-1-yl)benzonitrile derivatives (1a-p) was designed, synthesized, and identified as xanthine oxidase inhibitors with micromolar level potencies. Among them, the most promising compounds 1j and 1k were obtained with IC50 values of 8.1 and 6.7 μm, respectively. The Lineweaver-Burk plot revealed that compound 1k acted as a mixed-type xanthine oxidase inhibitor. SAR analysis revealed that a carbon atom occupying the X3 position is not as effective as a nitrogen atom, and an iso-pentyloxy or a cyclopentyloxy at the 2-position of benzonitrile moiety will benefit the inhibitory potency. The basis of xanthine oxidase inhibition by 1k was rationalized by molecular modeling studies.
-
Discovery and biological evaluation of some (1H-1,2,3-triazol-4-yl)methoxybenzaldehyde derivatives containing an anthraquinone moiety as potent xanthine oxidase inhibitors
Bioorganic and Medicinal Chemistry Letters, 2017Co-Authors: Ting-jian Zhang, Qing Xia Wu, Song-ye Li, Wei-yan Yuan, Su Yang, Qi Sun, Lin Wang, Fan-hao MengAbstract:A series of (1H-1,2,3-triazol-4-yl)methoxybenzaldehyde derivatives containing an anthraquinone moiety were synthesized and identified as novel xanthine oxidase inhibitors. Among them, the most promising compounds 1h and 1k were obtained with IC50values of 0.6 μM and 0.8 μM, respectively, which were more than 10-fold potent compared with allopurinol. The Lineweaver-Burk plot revealed that compound 1h acted as a mixed-type xanthine oxidase inhibitor. SAR analysis showed that the benzaldehyde moiety played a more important role than the anthraquinone moiety for inhibition potency. The basis of significant inhibition of xanthine oxidase by 1h was rationalized by molecular modeling studies.
Jun-sheng Luo - One of the best experts on this subject based on the ideXlab platform.
-
Cryptotanshinone and dihydrotanshinone I exhibit strong inhibition towards human liver microsome (HLM)-catalyzed propofol glucuronidation.
Fitoterapia, 2013Co-Authors: Ming Cong, Yun-feng Cao, Zhong-ze Fang, Shu-hong Tang, Jia-rui Wang, Jun-sheng LuoAbstract:Danshen is one of the most famous herbs in the world, and more and more danshen-prescribed drugs interactions have been reported in recent years. Evaluation of inhibition potential of danshen's major ingredients towards UDP-glucuronosyltransferases (UGTs) will be helpful for understanding detailed mechanisms for danshen-drugs interaction. Therefore, the aim of the present study is to investigate the inhibitory situation of cryptotanshinone and dihydrotanshinone I towards UGT enzyme-catalyzed propofol glucuronidation. In vitro the human liver microsome (HLM) incubation system was used, and the results showed that cryptotanshinone and dihydrotanshinone I exhibited dose-dependent inhibition towards HLM-catalyzed propofol glucuronidation. Dixon plot and Lineweaver-Burk plot showed that the inhibition type was best fit to competitive inhibition type for both cryptotanshinone and dihydrotanshinone I. The second plot using the slopes from the Lineweaver-Burk plot versus the concentrations of cryptotanshinone or dihydrotanshinone I was employed to calculate the inhibition parameters (Ki) to be 0.4 and 1.7μM, respectively. Using the reported maximum plasma concentration (Cmax), the altered in vivo exposure of propofol increased by 10% and 8.2% for the co-administration of dihydrotanshinone I and cryptotanshinone, respectively. All these results indicated the possible danshen-propofol interaction due to the inhibition of dihydrotanshinone I and cryptotanshinone towards the glucuronidation reaction of propofol.
Lingling Jing - One of the best experts on this subject based on the ideXlab platform.
-
purification and characterisation of a novel angiotensin i converting enzyme ace inhibitory peptide derived from the enzymatic hydrolysate of enteromorpha clathrata protein
Food Chemistry, 2016Co-Authors: Shujun Wang, Lingling JingAbstract:Abstract Hydrolysates containing angiotensin-I converting enzyme (ACE)-inhibitory peptide were prepared from Enteromorpha clathrata protein using alcalase. The hydrolysates were fractionated into two molecular-weight ranges (below and above 10 kDa) by ultrafiltration. The below-10 kDa fraction showed higher ACE-inhibitory activity and was subsequently purified by Sephadex G-15 gel filtration chromatography. The structure of active peptide was identified as Pro-Ala-Phe-Gly by HPLC-Q-TOF-MS and its IC50 value was 35.9 μM. The yield of this peptide from E. clathrata protein was 0.82%. Lineweaver–Burk plots demonstrated that the inhibitory kinetic mechanism of this peptide was non-competitive. Stability study revealed that the purified peptide showed resistance against gastrointestinal proteases. Thus, E. clathrata protein hydrolysate treated with alcalase is a beneficial ingredient of nutraceuticals and pharmaceuticals against hypertension and related diseases.
Ming Cong - One of the best experts on this subject based on the ideXlab platform.
-
Cryptotanshinone and dihydrotanshinone I exhibit strong inhibition towards human liver microsome (HLM)-catalyzed propofol glucuronidation.
Fitoterapia, 2013Co-Authors: Ming Cong, Yun-feng Cao, Zhong-ze Fang, Shu-hong Tang, Jia-rui Wang, Jun-sheng LuoAbstract:Danshen is one of the most famous herbs in the world, and more and more danshen-prescribed drugs interactions have been reported in recent years. Evaluation of inhibition potential of danshen's major ingredients towards UDP-glucuronosyltransferases (UGTs) will be helpful for understanding detailed mechanisms for danshen-drugs interaction. Therefore, the aim of the present study is to investigate the inhibitory situation of cryptotanshinone and dihydrotanshinone I towards UGT enzyme-catalyzed propofol glucuronidation. In vitro the human liver microsome (HLM) incubation system was used, and the results showed that cryptotanshinone and dihydrotanshinone I exhibited dose-dependent inhibition towards HLM-catalyzed propofol glucuronidation. Dixon plot and Lineweaver-Burk plot showed that the inhibition type was best fit to competitive inhibition type for both cryptotanshinone and dihydrotanshinone I. The second plot using the slopes from the Lineweaver-Burk plot versus the concentrations of cryptotanshinone or dihydrotanshinone I was employed to calculate the inhibition parameters (Ki) to be 0.4 and 1.7μM, respectively. Using the reported maximum plasma concentration (Cmax), the altered in vivo exposure of propofol increased by 10% and 8.2% for the co-administration of dihydrotanshinone I and cryptotanshinone, respectively. All these results indicated the possible danshen-propofol interaction due to the inhibition of dihydrotanshinone I and cryptotanshinone towards the glucuronidation reaction of propofol.