The Experts below are selected from a list of 273 Experts worldwide ranked by ideXlab platform
Youjun Zhou - One of the best experts on this subject based on the ideXlab platform.
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design and synthesis of phenylisoxazole derivatives as novel human Acrosin inhibitors
Bioorganic & Medicinal Chemistry Letters, 2014Co-Authors: Juntao Zhao, Wei Tian, Ju Zhu, Qianqian Chen, Youjun Zhou, Yang Liu, Yan Jiang, Guoqiang Dong, Heling Wang, Chun Quan ShengAbstract:Human Acrosin is an attractive target for the discovery of novel male contraceptives. Isoxazole derivative ISO-1, a small-molecule weak human Acrosin inhibitor, was used as the starting point for lead optimization. After two rounds of structure-based inhibitor design, a highly potent inhibitor B6 (IC50=1.44 μM) was successfully identified, which showed good selectivity over trypsin and represents one of the most active human Acrosin inhibitors up to date.
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synthesis and Acrosin inhibitory activities of 5 phenyl 1h pyrazole 3 carboxylic acid amide derivatives
Bioorganic & Medicinal Chemistry Letters, 2013Co-Authors: Wei Tian, Guangqian Han, Ju Zhu, Qianqian Chen, Juntao Zhao, Canhui Zheng, Ling Zhang, Youjun ZhouAbstract:A series of novel 5-phenyl-1H-pyrazole-3-carboxylic acid amide derivatives were designed, synthesized, and their Acrosin inhibitory activities in vitro were evaluated. The results of the Acrosin inhibitory activity showed that all target compounds were more potent than control TLCK. Compounds AQ-A1, AQ-D3, AQ-D4, AQ-E4 and AQ-E5 exhibited stronger Acrosin inhibitory activities than control ISO-1. Especially, compound AQ-E5 displayed the most potent Acrosin inhibitory activity in all the compounds, with an IC50 of 0.01μmol/mL. This study provided a new structural class for the development of novel Acrosin inhibitory agents.
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fragment based design of novel quinazolinon derivatives as human Acrosin inhibitors
Chemical Biology & Drug Design, 2013Co-Authors: Weiwei Ning, Ju Zhu, Canhui Zheng, Ling Zhang, Youjun Zhou, Xue Fei Liu, Yunlong Song, Xiaomeng Zhang, Chun Quan ShengAbstract:Human Acrosin is a promising target for the male contraceptives. On the basis of the active site of human Acrosin, a series of novel quinazolinon compounds were designed by a fragment docking and growing strategy. In vitro anti-Acrosin assay revealed that all the compounds showed potent human Acrosin inhibitory activities. In particular, compounds 5c and 5g are more active than the known inhibitors. Molecular docking studies revealed that the quinazolinon inhibitors interacted with human Acrosin mainly through hydrogen bonding and hydrophobic interactions. The binding mode was also consistent with the structure-activity relationships. The quinazolinon derivatives in this study can serve as new lead structure for the development of novel male contraceptives.
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design and synthesis of novel benzoheterocyclic derivatives as human Acrosin inhibitors by scaffold hopping
European Journal of Medicinal Chemistry, 2013Co-Authors: Qianqian Chen, Wei Tian, Guangqian Han, Ju Zhu, Juntao Zhao, Canhui Zheng, Youjun Zhou, Lili Ding, Chun Quan ShengAbstract:Human Acrosin is an attracting target for the development of novel male contraceptives. Scaffold hopping was used to optimize the isoxazolecarbaldehyde human Acrosin inhibitors and extend their structure-activity relationships. Four kinds of scaffolds, namely benzimidazole, benzothiazole, 3H-indazole, and 5-phenyl-1H-pyrazole, were designed and synthesized. Most of the synthesized compounds showed potent human Acrosin inhibitory activity and their binding modes were investigated by molecular docking. The scaffold of the compounds was found to be important for the inhibitory activity. Several compounds were more active than the positive control TLCK, suggesting that they can serve as good starting points for the discovery of novel male contraceptive agents.
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synthesis and Acrosin inhibitory activity of methyl 5 substituted 1h benzo d imidazol 2 yl carbamate derivatives
Bioorganic & Medicinal Chemistry Letters, 2012Co-Authors: Xue Fei Liu, Wei Tian, Guangqian Han, Ju Zhu, Qianqian Chen, Juntao Zhao, Yongzheng Fan, Lili Ding, Youjun ZhouAbstract:Abstract A series of novel methyl 5-substituted 1H-benzo[d]imidazol-2-ylcarbamates were designed, synthesized, and their Acrosin inhibitory activities evaluated in vitro. The results of Acrosin inhibitory activity showed that all title compounds were more potent than the control TLCK. Compound 4w displayed the most potent Acrosin inhibitory activity among all the compounds, with an IC50 of 6.3 × 10−5 M. The studies provide a new structural class for the development of novel Acrosin inhibitory agents.
Ju Zhu - One of the best experts on this subject based on the ideXlab platform.
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design and synthesis of phenylisoxazole derivatives as novel human Acrosin inhibitors
Bioorganic & Medicinal Chemistry Letters, 2014Co-Authors: Juntao Zhao, Wei Tian, Ju Zhu, Qianqian Chen, Youjun Zhou, Yang Liu, Yan Jiang, Guoqiang Dong, Heling Wang, Chun Quan ShengAbstract:Human Acrosin is an attractive target for the discovery of novel male contraceptives. Isoxazole derivative ISO-1, a small-molecule weak human Acrosin inhibitor, was used as the starting point for lead optimization. After two rounds of structure-based inhibitor design, a highly potent inhibitor B6 (IC50=1.44 μM) was successfully identified, which showed good selectivity over trypsin and represents one of the most active human Acrosin inhibitors up to date.
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synthesis and Acrosin inhibitory activities of 5 phenyl 1h pyrazole 3 carboxylic acid amide derivatives
Bioorganic & Medicinal Chemistry Letters, 2013Co-Authors: Wei Tian, Guangqian Han, Ju Zhu, Qianqian Chen, Juntao Zhao, Canhui Zheng, Ling Zhang, Youjun ZhouAbstract:A series of novel 5-phenyl-1H-pyrazole-3-carboxylic acid amide derivatives were designed, synthesized, and their Acrosin inhibitory activities in vitro were evaluated. The results of the Acrosin inhibitory activity showed that all target compounds were more potent than control TLCK. Compounds AQ-A1, AQ-D3, AQ-D4, AQ-E4 and AQ-E5 exhibited stronger Acrosin inhibitory activities than control ISO-1. Especially, compound AQ-E5 displayed the most potent Acrosin inhibitory activity in all the compounds, with an IC50 of 0.01μmol/mL. This study provided a new structural class for the development of novel Acrosin inhibitory agents.
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fragment based design of novel quinazolinon derivatives as human Acrosin inhibitors
Chemical Biology & Drug Design, 2013Co-Authors: Weiwei Ning, Ju Zhu, Canhui Zheng, Ling Zhang, Youjun Zhou, Xue Fei Liu, Yunlong Song, Xiaomeng Zhang, Chun Quan ShengAbstract:Human Acrosin is a promising target for the male contraceptives. On the basis of the active site of human Acrosin, a series of novel quinazolinon compounds were designed by a fragment docking and growing strategy. In vitro anti-Acrosin assay revealed that all the compounds showed potent human Acrosin inhibitory activities. In particular, compounds 5c and 5g are more active than the known inhibitors. Molecular docking studies revealed that the quinazolinon inhibitors interacted with human Acrosin mainly through hydrogen bonding and hydrophobic interactions. The binding mode was also consistent with the structure-activity relationships. The quinazolinon derivatives in this study can serve as new lead structure for the development of novel male contraceptives.
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design and synthesis of novel benzoheterocyclic derivatives as human Acrosin inhibitors by scaffold hopping
European Journal of Medicinal Chemistry, 2013Co-Authors: Qianqian Chen, Wei Tian, Guangqian Han, Ju Zhu, Juntao Zhao, Canhui Zheng, Youjun Zhou, Lili Ding, Chun Quan ShengAbstract:Human Acrosin is an attracting target for the development of novel male contraceptives. Scaffold hopping was used to optimize the isoxazolecarbaldehyde human Acrosin inhibitors and extend their structure-activity relationships. Four kinds of scaffolds, namely benzimidazole, benzothiazole, 3H-indazole, and 5-phenyl-1H-pyrazole, were designed and synthesized. Most of the synthesized compounds showed potent human Acrosin inhibitory activity and their binding modes were investigated by molecular docking. The scaffold of the compounds was found to be important for the inhibitory activity. Several compounds were more active than the positive control TLCK, suggesting that they can serve as good starting points for the discovery of novel male contraceptive agents.
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synthesis and Acrosin inhibitory activity of methyl 5 substituted 1h benzo d imidazol 2 yl carbamate derivatives
Bioorganic & Medicinal Chemistry Letters, 2012Co-Authors: Xue Fei Liu, Wei Tian, Guangqian Han, Ju Zhu, Qianqian Chen, Juntao Zhao, Yongzheng Fan, Lili Ding, Youjun ZhouAbstract:Abstract A series of novel methyl 5-substituted 1H-benzo[d]imidazol-2-ylcarbamates were designed, synthesized, and their Acrosin inhibitory activities evaluated in vitro. The results of Acrosin inhibitory activity showed that all title compounds were more potent than the control TLCK. Compound 4w displayed the most potent Acrosin inhibitory activity among all the compounds, with an IC50 of 6.3 × 10−5 M. The studies provide a new structural class for the development of novel Acrosin inhibitory agents.
Chun Quan Sheng - One of the best experts on this subject based on the ideXlab platform.
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design and synthesis of phenylisoxazole derivatives as novel human Acrosin inhibitors
Bioorganic & Medicinal Chemistry Letters, 2014Co-Authors: Juntao Zhao, Wei Tian, Ju Zhu, Qianqian Chen, Youjun Zhou, Yang Liu, Yan Jiang, Guoqiang Dong, Heling Wang, Chun Quan ShengAbstract:Human Acrosin is an attractive target for the discovery of novel male contraceptives. Isoxazole derivative ISO-1, a small-molecule weak human Acrosin inhibitor, was used as the starting point for lead optimization. After two rounds of structure-based inhibitor design, a highly potent inhibitor B6 (IC50=1.44 μM) was successfully identified, which showed good selectivity over trypsin and represents one of the most active human Acrosin inhibitors up to date.
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fragment based design of novel quinazolinon derivatives as human Acrosin inhibitors
Chemical Biology & Drug Design, 2013Co-Authors: Weiwei Ning, Ju Zhu, Canhui Zheng, Ling Zhang, Youjun Zhou, Xue Fei Liu, Yunlong Song, Xiaomeng Zhang, Chun Quan ShengAbstract:Human Acrosin is a promising target for the male contraceptives. On the basis of the active site of human Acrosin, a series of novel quinazolinon compounds were designed by a fragment docking and growing strategy. In vitro anti-Acrosin assay revealed that all the compounds showed potent human Acrosin inhibitory activities. In particular, compounds 5c and 5g are more active than the known inhibitors. Molecular docking studies revealed that the quinazolinon inhibitors interacted with human Acrosin mainly through hydrogen bonding and hydrophobic interactions. The binding mode was also consistent with the structure-activity relationships. The quinazolinon derivatives in this study can serve as new lead structure for the development of novel male contraceptives.
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design and synthesis of novel benzoheterocyclic derivatives as human Acrosin inhibitors by scaffold hopping
European Journal of Medicinal Chemistry, 2013Co-Authors: Qianqian Chen, Wei Tian, Guangqian Han, Ju Zhu, Juntao Zhao, Canhui Zheng, Youjun Zhou, Lili Ding, Chun Quan ShengAbstract:Human Acrosin is an attracting target for the development of novel male contraceptives. Scaffold hopping was used to optimize the isoxazolecarbaldehyde human Acrosin inhibitors and extend their structure-activity relationships. Four kinds of scaffolds, namely benzimidazole, benzothiazole, 3H-indazole, and 5-phenyl-1H-pyrazole, were designed and synthesized. Most of the synthesized compounds showed potent human Acrosin inhibitory activity and their binding modes were investigated by molecular docking. The scaffold of the compounds was found to be important for the inhibitory activity. Several compounds were more active than the positive control TLCK, suggesting that they can serve as good starting points for the discovery of novel male contraceptive agents.
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synthesis and Acrosin inhibitory activity of substituted 4 amino n diaminomethylene benzenesulfonamide derivatives
Bioorganic & Medicinal Chemistry Letters, 2011Co-Authors: Lili Ding, Guangqian Han, Ju Zhu, Juntao Zhao, Canhui Zheng, Xue Fei Liu, Chun Quan Sheng, Youjun ZhouAbstract:Abstract A series of new substituted 4-amino- N -(diaminomethylene) benzenesulfonamides were synthesized and their in vitro Acrosin inhibitory activities were evaluated. Most of the compounds showed potent Acrosin inhibitory activities with compounds 4o and 4p being significantly more potent than the control compound N -alpha-tosyl- l -lysyl-chloromethyl-ketone (TLCK). The compounds provide a new scaffold for the development of Acrosin inhibitory agents.
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discovery of novel human Acrosin inhibitors by virtual screening
Journal of Computer-aided Molecular Design, 2011Co-Authors: Xue Fei Liu, Ju Zhu, Canhui Zheng, Youjun Zhou, Guoqiang Dong, Jue Zhang, Chun Quan ShengAbstract:Human Acrosin is an attractive target for the discovery of male contraceptive drugs. For the first time, structure-based drug design was applied to discover structurally diverse human Acrosin inhibitors. A parallel virtual screening strategy in combination with pharmacophore-based and docking-based techniques was used to screen the SPECS database. From 16 compounds selected by virtual screening, a total of 10 compounds were found to be human Acrosin inhibitors. Compound 2 was found to be the most potent hit (IC50 = 14 μM) and its binding mode was investigated by molecular dynamics simulations. The hit interacted with human Acrosin mainly through hydrophobic and hydrogen-bonding interactions, which provided a good starting structure for further optimization studies.
Tadashi Baba - One of the best experts on this subject based on the ideXlab platform.
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p aminobenzamidine sensitive acrosomal protease s other than Acrosin serve the sperm penetration of the egg zona pellucida in mouse
Zygote, 1998Co-Authors: Kazuo Yamagata, Keitaro Murayama, Shinichi Kashiwabara, Nobuhisa Kohno, Tadashi BabaAbstract:It has been reported that a significant delay in protein dispersal from the acrosomal matrix is observed in wild-type sperm by adding p-aminobenzamidine, a trypsin/Acrosin inhibitor, to the incubation medium. The pattern of this delayed release was similar to that of the Acrosin-deficient mutant mouse sperm (Yamagata et al., J. Biol. Chem., 273, 10470-4, 1998). In the present study, no further delay in protein dispersal was found when the Acrosin-deficient sperm were treated with p-aminobenzamidine, indicating that among the p-aminobenzamidine-sensitive protease(s) only Acrosin may function to accelerate this process. Although the Acrosin-deficient sperm penetrated the zona pellucida (Baba et al., J. Biol. Chem., 269, 31845-9, 1994), the addition of p-aminobenzamidine to the fertilisation medium caused a significant inhibition of fertilisation in vitro. This indicates that there is a p-aminobenzamidine-sensitive protease(s) other than Acrosin participating in the zona penetration step. Indeed, we demonstrated that a non-Acrosin protease with a size of 42 kDa was present in the supernatant of the acrosome-reacted sperm suspension. The enzyme was inhibited by p-aminobenzamidine, diisopropyl fluorophosphate and N alpha-tosyl-L-lysine chloromethyl ketone, and was apparently activated by Acrosin.
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Acrosin accelerates the dispersal of sperm acrosomal proteins during acrosome reaction
Journal of Biological Chemistry, 1998Co-Authors: Kazuo Yamagata, Masaru Okabe, Keitaro Murayama, Kiyotaka Toshimori, Tomoko Nakanishi, Shinichi Kashiwabara, Tadashi BabaAbstract:Abstract Using homologous recombination, we have previously produced male mice carrying a disruptive mutation (Acr −/−) in the Acrosin gene. AlthoughAcr −/− mouse sperm lacking the Acrosin protease activity still penetrated the zona pellucida and fertilized the egg, the mutant sperm exhibited a delay in penetration of the zona pellucida solely at the early stages after insemination. To further elucidate the role of Acrosin in fertilization, we have examined the involvement of Acrosin in the acrosome reaction of sperm using theAcr −/− mutant mice. When the ability of sperm to adhere (attach) and bind to the zona pellucida of cumulus-free eggs was assessed in vitro, no significant difference was observed among Acr +/+,Acr +/−, and Acr −/−mouse sperm. Immunocytochemical analysis demonstrated that the release of several acrosomal proteins from the acrosome ofAcr −/− mouse sperm was significantly delayed during the calcium ionophore- and solubilized zona pellucida-induced acrosome reaction, despite normal membrane vesiculation. These data indicate that the delayed sperm penetration of the zona pellucida in the Acr −/− mouse results from the altered rate of protein dispersal from the acrosome and provide the first evidence that the major role of Acrosin is to accelerate the dispersal of acrosomal components during acrosome reaction.
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sperm from mice carrying a targeted mutation of the Acrosin gene can penetrate the oocyte zona pellucida and effect fertilization
Journal of Biological Chemistry, 1994Co-Authors: Tadashi Baba, Shinichi Kashiwabara, S Azuma, Yutaka ToyodaAbstract:The physiological function of mammalian sperm Acrosin has long been believed to be involved in the limited proteolysis of the oocyte zona pellucida, thus enabling the sperm to penetrate this extracellular matrix and to gain access to the oocyte plasma membrane. Here we show that male mice homozygous for a targeted mutation in the mouse Acrosin gene are still fertile in spite of the complete absence of Acrosin protease activity in the sperm. In vitro fertilization assays verified that sperm from the homozygous mutant mice penetrate the zona pellucida and effect fertilization. Therefore, Acrosin is not essential for both sperm penetration of the zona pellucida and fertilization.
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an acrosomal protein sp32 in mammalian sperm is a binding protein specific for two proAcrosins and an Acrosin intermediate
Journal of Biological Chemistry, 1994Co-Authors: Tadashi Baba, Shinichi Kashiwabara, Nobuhisa Kohno, Kunihiko Kodaira, Y Niida, Yuichi Michikawa, M Takenaka, George L Gerton, Yasuhito AraiAbstract:An acrosomal protein, sp32, was completely purified from acid extracts of ejaculated porcine sperm. Purified sp32 gave a single 32-kDa protein band on SDS-polyacrylamide gel electrophoresis and was characterized as a binding protein specific for 55-, 53-, and 49-kDa forms of (pro)Acrosin. This protein was not capable of binding a 43-kDa Acrosin intermediate and 35-kDa mature Acrosin. sp32 significantly accelerated autoactivation of proAcrosin at a basic pH in vitro and affected the maturation pathway of proAcrosin. In the presence of sp32, the 49-kDa Acrosin intermediate from the 55- and 53-kDa proAcrosins was accumulated, instead of the 43-kDa Acrosin intermediate. These results suggest that sp32 interacts with both the amino- and carboxyl-terminal sequences of the 53-kDa proAcrosin. The cDNA clones coding for porcine and guinea pig sp32 have been identified from testis cDNA libraries in lambda gt11. The deduced amino acid sequence indicates that sp32 is initially synthesized as a 61-kDa precursor protein with a putative signal peptide at the amino terminus. The carboxyl-terminal half of the precursor molecule corresponds to the mature sp32. Thus, sp32 is produced by post-translational modification of the precursor. The binding of sp32 to proAcrosin may be involved in packaging the Acrosin zymogen into the acrosomal matrix.
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structure and organization of the mouse Acrosin gene
Journal of Biochemistry, 1991Co-Authors: Ken Watanabe, Shinichi Kashiwabara, Tadashi Baba, Akiko Okamoto, Yuji AraiAbstract:The genomic region carrying the mouse Acrosin gene, including the 5'-flanking sequence, has been isolated and characterized. The Acrosin gene consists of five exons separated by four introns. Organization of this gene is very similar to those of the genes for other typical serine proteases, except for the phase class of the first intron. Riboprobe mapping and primer extension analyses showed that the start site of transcription initiation in the Acrosin gene is heterogeneous, including three major sites. Thus, the structure and organization of the mouse Acrosin gene are different from those of the human gene [Keime, S., Adham, I.M., & Engel, W. (1990) Eur. J. Biochem. 190, 195-200] in two respects: the number of transcription initiation sites and the phase class of the third intron. The putative promoter regions of the mouse and human Acrosin genes lack typical sequences of TATA, CAAT, and GC boxes, but contain a consensus sequence, GGGTGGG, known to be specific for the phosphoglycerate kinase-2 gene, and the protamine-1 and 2 genes that are uniquely expressed during spermatogenesis.
Canhui Zheng - One of the best experts on this subject based on the ideXlab platform.
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synthesis and Acrosin inhibitory activities of 5 phenyl 1h pyrazole 3 carboxylic acid amide derivatives
Bioorganic & Medicinal Chemistry Letters, 2013Co-Authors: Wei Tian, Guangqian Han, Ju Zhu, Qianqian Chen, Juntao Zhao, Canhui Zheng, Ling Zhang, Youjun ZhouAbstract:A series of novel 5-phenyl-1H-pyrazole-3-carboxylic acid amide derivatives were designed, synthesized, and their Acrosin inhibitory activities in vitro were evaluated. The results of the Acrosin inhibitory activity showed that all target compounds were more potent than control TLCK. Compounds AQ-A1, AQ-D3, AQ-D4, AQ-E4 and AQ-E5 exhibited stronger Acrosin inhibitory activities than control ISO-1. Especially, compound AQ-E5 displayed the most potent Acrosin inhibitory activity in all the compounds, with an IC50 of 0.01μmol/mL. This study provided a new structural class for the development of novel Acrosin inhibitory agents.
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fragment based design of novel quinazolinon derivatives as human Acrosin inhibitors
Chemical Biology & Drug Design, 2013Co-Authors: Weiwei Ning, Ju Zhu, Canhui Zheng, Ling Zhang, Youjun Zhou, Xue Fei Liu, Yunlong Song, Xiaomeng Zhang, Chun Quan ShengAbstract:Human Acrosin is a promising target for the male contraceptives. On the basis of the active site of human Acrosin, a series of novel quinazolinon compounds were designed by a fragment docking and growing strategy. In vitro anti-Acrosin assay revealed that all the compounds showed potent human Acrosin inhibitory activities. In particular, compounds 5c and 5g are more active than the known inhibitors. Molecular docking studies revealed that the quinazolinon inhibitors interacted with human Acrosin mainly through hydrogen bonding and hydrophobic interactions. The binding mode was also consistent with the structure-activity relationships. The quinazolinon derivatives in this study can serve as new lead structure for the development of novel male contraceptives.
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design and synthesis of novel benzoheterocyclic derivatives as human Acrosin inhibitors by scaffold hopping
European Journal of Medicinal Chemistry, 2013Co-Authors: Qianqian Chen, Wei Tian, Guangqian Han, Ju Zhu, Juntao Zhao, Canhui Zheng, Youjun Zhou, Lili Ding, Chun Quan ShengAbstract:Human Acrosin is an attracting target for the development of novel male contraceptives. Scaffold hopping was used to optimize the isoxazolecarbaldehyde human Acrosin inhibitors and extend their structure-activity relationships. Four kinds of scaffolds, namely benzimidazole, benzothiazole, 3H-indazole, and 5-phenyl-1H-pyrazole, were designed and synthesized. Most of the synthesized compounds showed potent human Acrosin inhibitory activity and their binding modes were investigated by molecular docking. The scaffold of the compounds was found to be important for the inhibitory activity. Several compounds were more active than the positive control TLCK, suggesting that they can serve as good starting points for the discovery of novel male contraceptive agents.
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synthesis and Acrosin inhibitory activity of substituted 4 amino n diaminomethylene benzenesulfonamide derivatives
Bioorganic & Medicinal Chemistry Letters, 2011Co-Authors: Lili Ding, Guangqian Han, Ju Zhu, Juntao Zhao, Canhui Zheng, Xue Fei Liu, Chun Quan Sheng, Youjun ZhouAbstract:Abstract A series of new substituted 4-amino- N -(diaminomethylene) benzenesulfonamides were synthesized and their in vitro Acrosin inhibitory activities were evaluated. Most of the compounds showed potent Acrosin inhibitory activities with compounds 4o and 4p being significantly more potent than the control compound N -alpha-tosyl- l -lysyl-chloromethyl-ketone (TLCK). The compounds provide a new scaffold for the development of Acrosin inhibitory agents.
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discovery of novel human Acrosin inhibitors by virtual screening
Journal of Computer-aided Molecular Design, 2011Co-Authors: Xue Fei Liu, Ju Zhu, Canhui Zheng, Youjun Zhou, Guoqiang Dong, Jue Zhang, Chun Quan ShengAbstract:Human Acrosin is an attractive target for the discovery of male contraceptive drugs. For the first time, structure-based drug design was applied to discover structurally diverse human Acrosin inhibitors. A parallel virtual screening strategy in combination with pharmacophore-based and docking-based techniques was used to screen the SPECS database. From 16 compounds selected by virtual screening, a total of 10 compounds were found to be human Acrosin inhibitors. Compound 2 was found to be the most potent hit (IC50 = 14 μM) and its binding mode was investigated by molecular dynamics simulations. The hit interacted with human Acrosin mainly through hydrophobic and hydrogen-bonding interactions, which provided a good starting structure for further optimization studies.
