Synthesis and biological evaluation of novel bavachinin analogs as anticancer agents
Synthesis and biological evaluation of novel bavachinin analogs as anticancer agents
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DOI：
10.1016/j.ejmech.2018.01.006
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发表时间：
2018-02-10
影响因子：
6.7
通讯作者：
Sangwan, Payare L.
中科院分区：
文献类型：
--
作者：
Gupta, Nidhi;Qayum, Arem;Sangwan, Payare L.
已经合成了 28 种补骨脂二氢黄酮类似物库，包括脂肪族和芳香族醚、环氧化物、查耳酮、肟、氨基脲、肟醚和三唑衍生物，并评估了其对四种不同人类癌细胞系的细胞毒性。生物评价研究显示，与补骨脂二氢黄酮类似物相比，许多类似物具有更好的细胞毒性。 1,2,3-三唑类似物 (17i) 对肺 (A549)、前列腺 (PC-3)、结肠 (HCT-116) 和乳腺癌 (MCF-7) 癌细胞系的 IC50 值分别为 7.72、16.08、7.13 和 11.67 μM。该类似物对 HCT-116 和 A549 细胞系的细胞毒性比母体分子提高了三倍和四倍 (1)。对所有合成类似物进行了结构活性关系（SAR）研究。此外，先导分子 (17i) 的机制研究表明，它可抑制人结肠癌细胞 (HCT-116) 的集落形成和体外迁移。此外，它还通过干扰线粒体膜电位 (MMP) 和 PARP 裂解来诱导 HCT-116 细胞的形态变化并介导细胞凋亡。 (C) 2018 Elsevier Masson SAS。版权所有。
A library of 28 analogs of bavachinin including aliphatic and aromatic ethers, epoxide, chalcone, oxime, semicarbazide, oxime ether and triazole derivatives have been synthesized and evaluated for cytotoxicity against four different human cancer cell lines. Bio-evaluation studies exhibited better cytotoxic profile for many analogs compare to bavachinin. Best results were observed for a 1,2,3-triazole analog (17i) with IC50 values 7.72,16.08, 7.13 and 11.67 mu M against lung (A549), prostate (PC-3), colon (HCT-116) and breast (MCF-7) cancer cell lines respectively. This analog showed three and four fold improvement in cytotoxicity against HCT-116 and A549 cell lines than parent molecule (1). Structure activity relationship (SAR) study for all synthesized analogs was carried out. Further, mechanistic study of the lead molecule (17i) revealed that it inhibits colony formation and in vitro migration of human colon cancer cells (HCT-116). Also, it induced the morphological changes and mediated the apoptotic cell death of HCT-116 cells with perturbance in mitochondrial membrane potential (MMP) and PARP cleavage. (C) 2018 Elsevier Masson SAS. All rights reserved.