Synthesis and Evaluationin vitroof Dihydrothiophenopyridine-Chalcone Derivatives as Anticancer Activity Agents

Abstract

摘要 以 2-噻吩乙胺与自制的查尔酮酸进行酰化反应得到酰胺类中间体 5a～5j, 经 Bischer-Napieralski 环合反应合成了 10 个未见报道的二氢噻吩并吡啶-查尔酮衍生物 6a～6j, 再经去氢反应获得 2 个噻吩并吡啶-查尔酮衍生物 7a 和 7b. 通 过噻唑蓝(MTT)法对 11 种细胞进行体外抗癌活性及安全性测试. 结果表明, 化合物 6a (p-F)、6d (o-Br)和 6h (m-OCH3) 对 HeLa、SGC-7901 细胞的抗癌活性优于紫杉醇. 当短时间处理(＜4 h)时, 6j (3,4,5-OCH3)在不影响正常细胞 MCF-10A 的情况下对癌细胞 MCF-7 显示强效抗癌效果, 值得进一步研究和开发.

Current scenario of chalcone hybrids with antibreast cancer therapeutic applications

“…Chalcone‐thiophene hybrids also demonstrated certain antiproliferative activity against breast cancer cells, but most of them were far inferior to the reference drugs. [ 71–78 ] Among them, chalcone‐benzothiophene hybrid 49 (IC 50 : 121 nM, CCK‐8 assay) showed potent antiproliferative activity against MCF‐7 cancer cells, but the activity was lower than that of combretastatin A‐4 (IC 50 : 11 nM). [ 71 ] Chalcone‐thieno[2,3‐ d ]pyrimidine hybrid 50 (IC 50 : 4.13 and 9.91 µM, MTT assay) was more potent than 5‐flurouracil (IC 50 : >20 and 10.22 µM) against MCF‐7 and MDA‐MB‐231 breast cancer cell lines, and mechanistically, hybrid 50 caused cell cycle arrest at sub‐G1 phase and induced apoptosis via the mitochondrial death pathway.…”

“…Chalcone-thiophene hybrids also demonstrated certain antiproliferative activity against breast cancer cells, but most of them were far inferior to the reference drugs. [71][72][73][74][75][76][77][78] Among them, chalconebenzothiophene hybrid 49 (IC 50 : 121 nM, CCK-8 assay) showed potent antiproliferative activity against MCF-7 cancer cells, but the activity was lower than that of combretastatin A-4 (IC 50 : 11 nM). [71] Chalcone-thieno [2,3-d] phase and induced apoptosis via the mitochondrial death pathway.…”