【摘 要】
：
A series of novel compounds(6a-6v)containing l-methylindol and 31-(4,5-dihydro-lH-pyraxol-1-yl)ethanone skeleton were designed,synthesized and biologically evaluated as potential tubulin polymerizatio
【机 构】
：
State Key Laboratory of Pharmaceutical Biotechnology,Nanjing University Nanjing 210093,People's Rep
【出 处】
：
第八届国际分子模拟与信息技术应用学术会议
论文部分内容阅读
A series of novel compounds(6a-6v)containing l-methylindol and 31-(4,5-dihydro-lH-pyraxol-1-yl)ethanone skeleton were designed,synthesized and biologically evaluated as potential tubulin polymerization inhibitors and anticancer agents.Among them,compound 6q showed the most potent tubulin polymerization inhibitory activity(IC50=1.98 μM)and in vitro growth inhibitory activity against A549,MCF-7 and HepG2 cell lines,with IC50 values of 0.15 μM,0.17 μM,and 0.25 μM respectively,being comparable to the positive control.Furthermore,compound 6q was a potent inducer of apoptosis in A549 cells and it had typical cellular effects for microtubule interacting agents,causing arrest of the cell cycle in G2/M phase,Confocal microscopy assay and molecular docking results further demonstrated that 6q could bind tightly to the colchicine-site of tubulin and act as an anti-tubulin agent.These studies,along with 3D-QSAR modeling provided an important basis for further optimization of compound 6q as a potential anticancer agent.
其他文献
Traditional Chinese medicine(TCM)is a multi-component and multi-target agent and could treat complex diseases in a holistic way,especially infection diseases.However,the underlying pharmacology remain
Metronidazole-sulfonamide derivatives 4a-4l,a new class of human carbonic anhydrase inhibitors(hCA),were designed,synthesized,isolated,and evaluated for their ability to inhibit the enzymatic activity
The aim of this study was to investigate the angiogenic effects of curcumin on an ischemia and lung cancer model.To induce ischemia combined with lung cancer models,unilateral femoral arteries of C57B
Background: Quantitative description of dose-response of a drug for complex systems is essential fortreatment of diseases and drug discovery.Given the growth of large-scale biological data obtained by
Cytochrome P450(CYP)17A1 is a dual-function monooxygenase with a critical role in the synthesis or many human steroid hormones The enzyme is an important target for Lrealment of breast and prostate ca
Anticoagulants and anti-platelet agents are simultaneously administrated in clinical practice(i.e.percutaneous coronary intervention),which cause significant risk of systemic bleeding.Targeted deliver
Fatty actci biosynthesis is essential for bacterial survival.FabH,β-ketoacyl-acyl carrier protein(ACP)synthase Ⅲ,is a particularly attractive target,since it is central to the initiation of fatty acid
Series of novel Schiffs base derivatives have been synthesized by combining 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl 4-formylbenzoate 5,6 with aromatic/heterocyclic amine 7a-r,8,9a-r in ethanol.All
A series of aryl-2H-pyrazole derivatives were synthesized and evaluated for inhibitory activity against xanthine oxidase in vitro as potent xanthine oxidase inhibitors.Among them,2 aryl-2H-pyrazole de
A series of 1-methyl-1H-indole-pyrazoline hybrids were designed,synthesized,and biologically evaluated as potential tubulin polymerization inhibitors.Among them,compound e19 [5-(5-bromo-1-methyl-1H-in