The Experts below are selected from a list of 1710 Experts worldwide ranked by ideXlab platform
Wen Luo - One of the best experts on this subject based on the ideXlab platform.
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design synthesis and evaluation of novel 7 aminoalkyl substituted flavonoid derivatives with improved cholinesterase inhibitory activities
Bioorganic & Medicinal Chemistry, 2016Co-Authors: Wen Luo, Chen Hong, Ying Chen, Ting Wang, Liping Chang, Congcong Chang, Yacheng Yang, Songqiang Xie, Chao-jie WangAbstract:Abstract A novel series of 7-aminoalkyl-substituted flavonoid derivatives 5a–5r were designed, synthesized and evaluated as potential cholinesterase inhibitors. The results showed that most of the synthesized compounds exhibited potent acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities at the micromolar range. Compound 2-(naphthalen-1-yl)-7-(8-(pyrrolidin-1-yl)octyloxy)-4H-chromen-4-one (5q) showed the best inhibitory activity (IC50, 0.64 μM for AChE and 0.42 μM for BChE) which were better than our previously reported compounds and the commercially available cholinergic agent Rivastigmine. The results from a Lineweaver–Burk Plot indicated a mixed-type inhibition for compound 5q with AChE and BChE. Furthermore, molecular modeling study showed that 5q targeted both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE. Besides, these compounds (5a–5r) did not affect PC12 and HepG2 cell viability at the concentration of 10 μM. Consequently, these flavonoid derivatives should be further investigated as multipotent agents for the treatment of Alzheimer’s disease.
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Design, synthesis and evaluation of genistein-polyamine conjugates as multi-functional anti-Alzheimer agents
Acta Pharmaceutica Sinica B, 2015Co-Authors: Xin Zhang, Jiang Wang, Wen Luo, Chen Hong, Chao-jie WangAbstract:A series of genistein-polyamine conjugates (4a-4h) were designed, synthesized and evaluated as multi-functional anti-Alzheimer agents. The results showed that these compounds had significant cholinesterases (ChEs) inhibitory activity. Compound 4b exhibited the strongest inhibition to acetylcholinesterase (AChE) with an IC50value of 2.75μmol/L, which was better than that of rivastigmine (5.60μmol/L). Lineweaver-Burk Plot and molecular modeling study showed that compound 4b targeted both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE. Besides, compound 4b showed potent metal-chelating ability. In addition, it was found that 4a-4h did not affect HepG-2 cell viability at the concentration of 10μmol/L.
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design synthesis and evaluation of novel 4 dimethylamine flavonoid derivatives as potential multi functional anti alzheimer agents
Bioorganic & Medicinal Chemistry, 2013Co-Authors: Wen Luo, Chen Hong, Runguo Tian, Yueqiao Wang, Junjie Yue, Chao-jie WangAbstract:A series of 4-dimethylamine flavonoid derivatives 5a-5r were designed, synthesized and evaluated as potential multi-functional anti-Alzheimer agents. The results showed that most of the synthesized compounds exhibited high acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activity at the micromolar range (IC50, 1.83-33.20 μM for AChE and 0.82-11.45 μM for BChE). A Lineweaver-Burk Plot indicated a mixed-type inhibition for compound 5j with AChE, and molecular modeling study showed that 5j targeted both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE. Besides, the derivatives showed potent self-induced Aβ aggregation inhibitory activity at 20 μM with percentage from 25% to 48%. In addition, some compounds (5j-5q) showed potent oxygen radical absorbance capacity (ORAC) ranging from 1.5- to 2.6-fold of the Trolox value. These compounds should be further investigated as multi-potent agents for the treatment of Alzheimer's disease.
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Synthesis and evaluation of heterobivalent tacrine derivatives as potential multi-functional anti-Alzheimer agents.
European journal of medicinal chemistry, 2011Co-Authors: Wen Luo, Shi-liang Huang, Zhi-shu HuangAbstract:A new series of heterobivalent tacrine derivatives were designed, synthesized and evaluated as potential multi-functional anti-Alzheimer agents for their inhibitory activity on cholinesterases, antioxidant activity and self-induced β-amyloid (Aβ) aggregation. All these synthesized compounds had potent inhibition activity on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) at nanomolar range. A Lineweaver-Burk Plot and molecular modeling study showed that these compounds targeted both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE. The compounds containing hydroxyl group showed potent peroxyl radical absorbance activity. In addition, compound 5j exhibited higher self-induced Aβ aggregation inhibitory activity than curcumin, which could become a multi-functional agent for further development for the treatment of AD.
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design synthesis and evaluation of novel tacrine multialkoxybenzene hybrids as dual inhibitors for cholinesterases and amyloid beta aggregation
Bioorganic & Medicinal Chemistry, 2011Co-Authors: Wen Luo, Shi-liang Huang, Jiaheng Tan, Zhi-shu HuangAbstract:A new series of tacrine-multialkoxybenzene hybrids (9a-9n) were designed, synthesized and evaluated as dual inhibitors of cholinesterases (ChEs) and self-induced β-amyloid (Aβ) aggregation. All the synthesized compounds had high acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory activity with IC₅₀ values at the nanomolar range, which were much better than tacrine alone. A Lineweaver-Burk Plot and molecular modeling study showed that these hybrids targeted both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE. Besides, compounds 9a-9f with methylenedioxybenzene moiety showed higher self-induced Aβ aggregation inhibitory activity than a reference compound, curcumin. These compounds could be selected as multi-potent agents for further investigation to treat AD.
Fan-hao Meng - One of the best experts on this subject based on the ideXlab platform.
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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.
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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.
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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.
Chao-jie Wang - One of the best experts on this subject based on the ideXlab platform.
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design synthesis and evaluation of novel 7 aminoalkyl substituted flavonoid derivatives with improved cholinesterase inhibitory activities
Bioorganic & Medicinal Chemistry, 2016Co-Authors: Wen Luo, Chen Hong, Ying Chen, Ting Wang, Liping Chang, Congcong Chang, Yacheng Yang, Songqiang Xie, Chao-jie WangAbstract:Abstract A novel series of 7-aminoalkyl-substituted flavonoid derivatives 5a–5r were designed, synthesized and evaluated as potential cholinesterase inhibitors. The results showed that most of the synthesized compounds exhibited potent acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities at the micromolar range. Compound 2-(naphthalen-1-yl)-7-(8-(pyrrolidin-1-yl)octyloxy)-4H-chromen-4-one (5q) showed the best inhibitory activity (IC50, 0.64 μM for AChE and 0.42 μM for BChE) which were better than our previously reported compounds and the commercially available cholinergic agent Rivastigmine. The results from a Lineweaver–Burk Plot indicated a mixed-type inhibition for compound 5q with AChE and BChE. Furthermore, molecular modeling study showed that 5q targeted both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE. Besides, these compounds (5a–5r) did not affect PC12 and HepG2 cell viability at the concentration of 10 μM. Consequently, these flavonoid derivatives should be further investigated as multipotent agents for the treatment of Alzheimer’s disease.
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Design, synthesis and evaluation of genistein-polyamine conjugates as multi-functional anti-Alzheimer agents
Acta Pharmaceutica Sinica B, 2015Co-Authors: Xin Zhang, Jiang Wang, Wen Luo, Chen Hong, Chao-jie WangAbstract:A series of genistein-polyamine conjugates (4a-4h) were designed, synthesized and evaluated as multi-functional anti-Alzheimer agents. The results showed that these compounds had significant cholinesterases (ChEs) inhibitory activity. Compound 4b exhibited the strongest inhibition to acetylcholinesterase (AChE) with an IC50value of 2.75μmol/L, which was better than that of rivastigmine (5.60μmol/L). Lineweaver-Burk Plot and molecular modeling study showed that compound 4b targeted both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE. Besides, compound 4b showed potent metal-chelating ability. In addition, it was found that 4a-4h did not affect HepG-2 cell viability at the concentration of 10μmol/L.
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design synthesis and evaluation of novel 4 dimethylamine flavonoid derivatives as potential multi functional anti alzheimer agents
Bioorganic & Medicinal Chemistry, 2013Co-Authors: Wen Luo, Chen Hong, Runguo Tian, Yueqiao Wang, Junjie Yue, Chao-jie WangAbstract:A series of 4-dimethylamine flavonoid derivatives 5a-5r were designed, synthesized and evaluated as potential multi-functional anti-Alzheimer agents. The results showed that most of the synthesized compounds exhibited high acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activity at the micromolar range (IC50, 1.83-33.20 μM for AChE and 0.82-11.45 μM for BChE). A Lineweaver-Burk Plot indicated a mixed-type inhibition for compound 5j with AChE, and molecular modeling study showed that 5j targeted both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE. Besides, the derivatives showed potent self-induced Aβ aggregation inhibitory activity at 20 μM with percentage from 25% to 48%. In addition, some compounds (5j-5q) showed potent oxygen radical absorbance capacity (ORAC) ranging from 1.5- to 2.6-fold of the Trolox value. These compounds should be further investigated as multi-potent agents for the treatment of Alzheimer's disease.
Ting-jian Zhang - One of the best experts on this subject based on the ideXlab platform.
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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.
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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.
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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.
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synthesis and evaluation of 1 hydroxy methoxy 4 methyl 2 phenyl 1h imidazole 5 carboxylic acid derivatives as non purine xanthine oxidase inhibitors
European Journal of Medicinal Chemistry, 2015Co-Authors: Shaolei Chen, Ting-jian Zhang, Jian Wang, Fangyang Wang, Handong Niu, Shaojie WangAbstract:Xanthine oxidase is a key enzyme that catalyses hypoxanthine and xanthine to uric acid, whose overproduction leads to the gout-causing hyperuricemia. In this study, a series of 1-hydroxy/methoxy-4-methyl-2-phenyl-1H-imidazole-5-carboxylic acid derivatives (4a-4k and 6a-6k) was synthesized and evaluated for their inhibitory potency against xanthine oxidase. The 1-hydroxyl substituted derivatives 4a-4k showed excellent inhibitory potency with IC50 values ranging from 0.003 μM to 1.2 μM, with compounds 4d (IC₅₀ = 0.003 μM), 4e (IC₅₀ = 0.003 μM), and 4f (IC₅₀ = 0.006 μM) manifesting the most potent xanthine oxidase inhibitory potency that were comparable with that of Febuxostat (IC₅₀ = 0.01 μM). Lineweaver-Burk Plot analysis revealed that representative compound 4f acted as a mixed-type inhibitor for xanthine oxidase. The basis of significant inhibition of xanthine oxidase by 4f was rationalized by its molecular docking into the active site of xanthine dehydrogenase.
Zhi-shu Huang - One of the best experts on this subject based on the ideXlab platform.
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Synthesis and evaluation of heterobivalent tacrine derivatives as potential multi-functional anti-Alzheimer agents.
European journal of medicinal chemistry, 2011Co-Authors: Wen Luo, Shi-liang Huang, Zhi-shu HuangAbstract:A new series of heterobivalent tacrine derivatives were designed, synthesized and evaluated as potential multi-functional anti-Alzheimer agents for their inhibitory activity on cholinesterases, antioxidant activity and self-induced β-amyloid (Aβ) aggregation. All these synthesized compounds had potent inhibition activity on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) at nanomolar range. A Lineweaver-Burk Plot and molecular modeling study showed that these compounds targeted both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE. The compounds containing hydroxyl group showed potent peroxyl radical absorbance activity. In addition, compound 5j exhibited higher self-induced Aβ aggregation inhibitory activity than curcumin, which could become a multi-functional agent for further development for the treatment of AD.
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design synthesis and evaluation of novel tacrine multialkoxybenzene hybrids as dual inhibitors for cholinesterases and amyloid beta aggregation
Bioorganic & Medicinal Chemistry, 2011Co-Authors: Wen Luo, Shi-liang Huang, Jiaheng Tan, Zhi-shu HuangAbstract:A new series of tacrine-multialkoxybenzene hybrids (9a-9n) were designed, synthesized and evaluated as dual inhibitors of cholinesterases (ChEs) and self-induced β-amyloid (Aβ) aggregation. All the synthesized compounds had high acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory activity with IC₅₀ values at the nanomolar range, which were much better than tacrine alone. A Lineweaver-Burk Plot and molecular modeling study showed that these hybrids targeted both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE. Besides, compounds 9a-9f with methylenedioxybenzene moiety showed higher self-induced Aβ aggregation inhibitory activity than a reference compound, curcumin. These compounds could be selected as multi-potent agents for further investigation to treat AD.