赫拉
悉尼酮
化学
Jurkat细胞
碘化丙啶
细胞凋亡
MTT法
广告
癌细胞
分子生物学
癌症研究
生物化学
生物
程序性细胞死亡
细胞
癌症
免疫学
体外
有机化学
T细胞
遗传学
戒指(化学)
免疫系统
作者
Syed Lidia Hossain,Manoj Mathews,Veerabhadra Swamy Bhyranalyar Nagarajappa,B Kiran Kumar,Channabasa Veshwar Veerappa Yelamaggad,C. Rajendra Singh
标识
DOI:10.4103/jcrt.jcrt_1614_20
摘要
To evaluate the antiproliferative and apoptosis inducing activity of different sydnones on cancer cell lines and their interaction with cancer proteins by molecular docking studies.Antiproliferative activity was carried out by MTT assay and apoptosis inducing activity was performed by DAPI and Annexin V and propidium iodide staining. Molecular docking studies were performed using AutoDock Tools 1.5.6. Pharmacokinetics properties like ADME and toxicity were analysed by pkCSM web server.In this study, four new sydnone compounds 3-(4-nonylbiphenyl-4'-yl) sydnone (MC-182), 3-(4-propylbiphenyl-4'-yl) sydnone (MC-454), 3-(4-hexylbiphenyl-4'-yl) sydnone (MC-433), and 3-(4-methylbiphenyl-4'-yl) sydnone (MC-431) were screened for antiproliferative and apoptotic effect against BT-474 (human breast cancer), HeLa (human cervical cancer) and Jurkat (human myeloid leukemia) Mostly, all the sydnone compounds exhibited decent antiproliferative effectiveness, but compound MC-431, MC-433, and MC-454 showed more antiproliferative activity (IC50 1.71, 10.09 and 2.87 μM against BT-474, Hela and Jurkat cell line, respectively). The changes of morphological characteristics of cancer cells determined by staining techniques indicate the apoptotic cell death. The molecular docking and interaction studies were carried out between sydnones with cancer proteins (epidermal growth factor domain receptor tyrosine kinase [EGF-TK], tumor necrosis factor-alpha [TNF-α] and Caspase3. Among all four sydnone molecules, two compounds MC-454 and MC-431 showed good binding energy with targeted proteins. Drug-like property was predicted by ADME toxicity study.The results indicate sydnone compounds were found to exhibit anticancer activity by inducing apoptosis. The molecular docking study of sydnones with cancer proteins showed a decent interaction affinity. The results of absorption, distribution, metabolism, excretion and toxicity studies by the Insilco approach also proved that MC-454 sydnone showed better In-Vivo administration. Thus, the current research work indicates that these sydnone compounds would be prospective in developing anticancer medicines.
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