苯并咪唑-氧吲哚共轭物的合成及作为微管靶向剂的生物评价。
Synthesis and biological evaluation of benzimidazole-oxindole conjugates as microtubule-targeting agents.
机构信息
Medicinal Chemistry and Pharmacology, CSIR - Indian Institute of Chemical Technology, Hyderabad 500007, India; Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India.
Medicinal Chemistry and Pharmacology, CSIR - Indian Institute of Chemical Technology, Hyderabad 500007, India.
出版信息
Bioorg Chem. 2015 Dec;63:72-84. doi: 10.1016/j.bioorg.2015.09.003. Epub 2015 Oct 8.
A series of benzimidazole-oxindole conjugates were synthesized and evaluated for their cytotoxic activity. The cytotoxicity assay results suggest that conjugates 5c and 5p exhibit promising cytotoxicity against human breast cancer cell line (MCF-7). The Cell cycle analysis revealed that these conjugates induced cell cycle arrest at G2/M phase in MCF-7 cells. The tubulin polymerization assay results suggested that these conjugates inhibit tubulin polymerization with IC50 values 1.12 and 1.59μM respectively. Immunofluorescence analysis also suggested that these conjugates effectively inhibited the microtubule assembly in MCF-7 cells. Further, molecular docking studies indicated that these conjugates 5c and 5p interact and binds efficiently with the tubulin protein. By and large, the results demonstrated that these benzimidazole-oxindole conjugates possess cytotoxic property by inhibiting the tubulin polymerization.
一系列苯并咪唑-氧吲哚缀合物被合成并评估其细胞毒性活性。细胞毒性测定结果表明，化合物 5c 和 5p 对人乳腺癌细胞系（MCF-7）表现出有希望的细胞毒性。细胞周期分析表明，这些缀合物在 MCF-7 细胞中诱导细胞周期停滞在 G2/M 期。微管聚合测定结果表明，这些缀合物分别以 IC50 值 1.12 和 1.59μM 抑制微管聚合。免疫荧光分析还表明，这些缀合物有效地抑制了 MCF-7 细胞中的微管组装。进一步的分子对接研究表明，这些化合物 5c 和 5p 与微管蛋白有效相互作用和结合。总的来说，这些结果表明，这些苯并咪唑-氧吲哚缀合物通过抑制微管聚合具有细胞毒性。
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