康普瑞他汀连接的1,3,4-恶二唑共轭物作为有效的微管蛋白聚合抑制剂。
Combretastatin linked 1,3,4-oxadiazole conjugates as a Potent Tubulin Polymerization inhibitors.
作者信息
Kamal Ahmed, Srikanth P S, Vishnuvardhan M V P S, Kumar G Bharath, Suresh Babu Korrapati, Hussaini S M Ali, Kapure Jeevak Sopanrao, Alarifi Abdullah
机构信息
Medicinal Chemistry and Pharmacology, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India; Academy of Scientific and Innovative Research, CSIR-Indian Institute of Chemical Technology, Hyderabad, India; Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India; Catalytic Chemistry Chair, Chemistry Department, College of Science, King Saud University, Riyadh 11451, Saudi Arabia.
Medicinal Chemistry and Pharmacology, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India; Academy of Scientific and Innovative Research, CSIR-Indian Institute of Chemical Technology, Hyderabad, India.
出版信息
Bioorg Chem. 2016 Apr;65:126-36. doi: 10.1016/j.bioorg.2016.02.007. Epub 2016 Feb 26.
A new class of combretastatin linked 1,3,4-oxadiazoles were designed, synthesized and screened for their cytotoxic activity against five human cancer cell lines such as HeLa, DU-145, A549, MDA-MB-231 and B16. These compounds showed significant cytotoxicity with IC50 values in the range 0.118-54.32μM. Conjugate 5m displayed potent antiproliferative activity against DU-145 cell line. Flow cytometric analysis revealed that these compounds arrested the cell cycle in G2/M phase. Moreover, the tubulin polymerization assay and immunofluorescence analysis indicate that 5m exhibits potent inhibitory effect on the tubulin assembly. Further, DNA fragmentation and Hoecst staining assays confirm that 5m induces apoptosis. Molecular docking studies and competitive binding assay indicated that 5m effectively bind at the colchicine binding site of the tubulin.
设计、合成了一类新型的与康普瑞他汀相连的1,3,4-恶二唑，并对其针对五种人类癌细胞系（如HeLa、DU-145、A549、MDA-MB-231和B16）的细胞毒性活性进行了筛选。这些化合物表现出显著的细胞毒性，IC50值在0.118 - 54.32μM范围内。共轭物5m对DU-145细胞系显示出强大的抗增殖活性。流式细胞术分析表明，这些化合物使细胞周期停滞在G2/M期。此外，微管蛋白聚合试验和免疫荧光分析表明，5m对微管蛋白组装具有强大的抑制作用。进一步地，DNA片段化和Hoecst染色试验证实5m诱导细胞凋亡。分子对接研究和竞争性结合试验表明，5m在微管蛋白的秋水仙碱结合位点有效结合。
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