Publications (9)29.49 Total impact
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Article: Fragment-based Design of Novel Quinazolinon Derivatives as Human Acrosin Inhibitors.
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ABSTRACT: 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. © 2013 John Wiley & Sons A/S.Chemical Biology & Drug Design 01/2013; · 2.28 Impact Factor -
Article: Design and synthesis of novel benzoheterocyclic derivatives as human acrosin inhibitors by scaffold hopping.
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ABSTRACT: 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.European journal of medicinal chemistry 11/2012; 59C:176-182. · 3.27 Impact Factor -
Article: Synthesis and biological evaluation of 1-benzylidene-3,4-dihydronaphthalen-2-one as a new class of microtubule-targeting agents.
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ABSTRACT: A series of 1-benzylidene-3,4-dihydronaphthalen-2-one derivatives were designed and synthesized, and their biological activities in vitro and in vivo were evaluated. The results showed a number of the title compounds exhibiting potent nanomolar activity in several human cancer cell lines. Of these, compound 22b showed the strongest inhibitory activity against human CEM, MDA-MBA-435, and K562 cells (IC(50) = 1 nM), displayed in vitro inhibition of tubulin polymerization (IC(50) = 3.93 μM), and significantly induced cell cycle arrest in G2/M phase. In addition, compound 22b could inhibit the tumor growth in colon nude mouse xenograft tumor model significantly and seemed safer than CA-4 when achieving a similar tumor suppression. This study provided a new molecular scaffold for the further development of antitumor agents that target tubulin.Journal of Medicinal Chemistry 06/2012; 55(12):5720-33. · 4.80 Impact Factor -
Article: Synthesis and acrosin inhibitory activity of substituted 4-amino-N-(diaminomethylene) benzenesulfonamide derivatives.
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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.Bioorganic & medicinal chemistry letters 11/2011; 21(22):6674-7. · 2.65 Impact Factor -
Article: Synthesis and acrosin inhibitory activities of substituted ethyl 5-(4-aminophenyl)-1H-pyrazole-3-carboxylate derivatives.
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ABSTRACT: A series of novel ethyl 5-(4-aminophenyl)-1H-pyrazole-3-carboxylate derivatives were designed and synthesized and their in vitro acrosin inhibitory activities were evaluated. Most of the compounds exhibited acrosin inhibitory activities. Among them, three compounds (5l, 5n, and 5v) were more potent than that of the control TLCK. These provide a new structural type for the development of novel contraceptive acrosin inhibitory agents.Bioorganic & medicinal chemistry letters 10/2011; 21(19):5822-5. · 2.65 Impact Factor -
Article: Discovery of novel human acrosin inhibitors by virtual screening.
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ABSTRACT: 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 (IC(50) = 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.Journal of Computer-Aided Molecular Design 10/2011; 25(10):977-85. · 3.39 Impact Factor -
Article: Synthesis and antifungal activities in vitro of novel pyrazino [2,1-a] isoquinolin derivatives.
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ABSTRACT: A series of novel pyrazino[2,1-a]isoquinolin compounds were designed and synthesized, and their antifungal activities in vitro were evaluated. The results showed that all of the compounds exhibited antifungal activities. Some of them exhibited stronger antifungal activities than that of lead compounds and among them compound 11b was the most potent one, which showed more potent than that of the active control fluconazole to the four of the five tested fungi. The studies presented here provide a new structural type for the development of novel antifungal agents.Bioorganic & medicinal chemistry letters 02/2010; 20(3):979-82. · 2.65 Impact Factor -
Article: Synthesis and antifungal activities of novel 2-aminotetralin derivatives.
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ABSTRACT: Novel 2-aminotetralin derivatives were synthesized as antifungal agents. The 2-aminotetralin scaffold was chemically designed to mimic the tetrahydroisoquinoline ring of the lead molecule described before. Their antifungal activities were evaluated in vitro by measuring the minimal inhibitory concentrations (MICs). Compounds 10a, 12a, 12c, 13b, and 13d are more potent than fluconazole against seven testing human fungal pathogens. Compound 10b exhibits much higher antifungal activities against all of the four fluconazole-resistant clinic Candida albicans strains than the control drugs including amphotericin B, terbinafine, ketoconazole, and itraconazole. The mode of action of some compounds to the potential receptor lanosterol 14alpha-demethylase (CYP51) was investigated by molecular docking. The studies presented here provide a new structural type for the development of novel antifungal compounds. Furthermore, 10b was evaluated in vivo by a rat vaginal candidiasis model, and it was found that 10b significantly decreases the number of fungal colony counts.Journal of Medicinal Chemistry 12/2007; 50(22):5293-300. · 5.25 Impact Factor -
Article: Design, synthesis, and antifungal activities in vitro of novel tetrahydroisoquinoline compounds based on the structure of lanosterol 14alpha-demethylase (CYP51) of fungi.
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ABSTRACT: Novel tetrahydroisoquinoline compounds were designed by coupling structure-based de novo design based on the structure of lanosterol 14alpha-demethylase (CYP51). The chemical synthesis and the antifungal activities in vitro of them were reported. The results exhibited that all of the lead compounds showed potent antifungal activities, in which compounds 6 and 7 had equal or stronger antifungal activities against five test fungi than that of fluconazole. The studies presented here provided the antifungal lead compounds. The affinity of the lead molecules for CYP51 was mainly attributed to their non-bonding interaction with the apoprotein, which was different from the azole antifungal agents.Bioorganic & Medicinal Chemistry Letters 11/2006; 16(20):5285-9. · 2.55 Impact Factor
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Institutions
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2006
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Second Military Medical University, Shanghai
Shanghai, Shanghai Shi, China
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