Department of Applied Chemistry, Kyushu Institute of Technology1-1 Sensuicho, Tobata, Kitakyushu 804-8550, Japan; Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
Bioorg Med Chem. 2019 Oct 1;27(19):115026. doi: 10.1016/j.bmc.2019.07.042. Epub 2019 Jul 30.
A series of new isoxazolyl, triazolyl and phenyl based 3-thiophen-2-yl-quinoline derivatives were synthesized adopting click chemistry approach. In addition, the synthesis of new useful synthon, (2-chloroquinolin-3-yl) (thiophen-2-yl) methanol, is reported. The obtained compounds were characterized by spectral data analysis and evaluated for their anticancer activity. All the derivatives were subjected to in vitro MTT cytotoxicity screening assay against a panel of four different human cancer cell lines, liver (HepG-2), colon (HCT-116), human cervical cancer (HeLa) and breast (MCF-7). Out of a library of 17 compounds, two compounds have been identified as potent and selective cytotoxic agents against HeLa and MCF-7 cell lines. SAR studies for such hybridized analogues were investigated and phenyl derivatives were proved to be more potent than isoxazole and triazole derivatives. Furthermore, the promising compounds were selected for in vitro inhibition of EGFR-TK and Topo II enzymes. Also, they were subjected to cell cycle arrest analysis and apoptosis assay on MCF-7 cells. Our recent finding highlights these thiophene-quinoline analogues as a promising class of compounds for further studies concerning new anticancer therapies.
采用点击化学方法合成了一系列新的异噁唑基、三唑基和苯基 3-噻吩-2-基喹啉衍生物。此外，还报道了新的有用前体（2-氯喹啉-3-基）（噻吩-2-基）甲醇的合成。所得化合物通过光谱数据分析进行了表征，并评估了它们的抗癌活性。所有衍生物均进行了体外 MTT 细胞毒性筛选试验，以评估其对四种不同人癌细胞系（肝（HepG-2）、结肠（HCT-116）、人宫颈癌（HeLa）和乳腺癌（MCF-7））的抗癌活性。在 17 种化合物库中，有两种化合物被鉴定为针对 HeLa 和 MCF-7 细胞系的有效和选择性细胞毒性剂。对这些杂化类似物进行了 SAR 研究，结果表明苯基衍生物比异噁唑和三唑衍生物更有效。此外，选择有前途的化合物用于体外抑制 EGFR-TK 和拓扑异构酶 II 酶。还对 MCF-7 细胞进行了细胞周期阻滞分析和凋亡测定。我们最近的发现强调了这些噻吩-喹啉类似物作为一类有前途的化合物，可进一步研究新的抗癌疗法。
