Abstract

A new series of 2-alkylthio-N-(quinazolin-2-yl)benzenesulfonamide derivatives have been synthesized and evaluated in vitro for their antiproliferative activity by MTT assay against cancer cell lines HCT-116, MCF-7, and HeLa as well as the NCI-60 human tumor cell lines screen. In NCI screen, three compounds inhibited approximately 50% growth of RPMI-8226 and A549/ATCC cell lines. The mean of IC₅₀ calculated in MTT assays for three tested cell lines was about 45 μM for four compounds. The QSAR allowed finding statistically significant OPLS models for HeLa cell line. Metabolic stability in vitro studies indicated favorable and unfavorable structural elements. The good metabolic stability, with t_1/2 higher than 40 min, was observed for three derivatives, which together with their antiproliferative activity and good ADMET profile, makes them good leading structures for further research.

Graphical abstract

中文翻译：

---

2-烷硫基-N-(喹唑啉-2-基)苯磺酰胺衍生物的合成：抗癌活性、QSAR 研究和代谢稳定性。

摘要

合成了一系列新的 2-烷硫基-N- (喹唑啉-2-基)苯磺酰胺衍生物，并通过 MTT 法在体外评估了它们对癌细胞系 HCT-116、MCF-7 和 HeLa 以及NCI-60 人类肿瘤细胞系筛选。在 NCI 筛选中，三种化合物抑制了大约 50% 的 RPMI-8226 和 A549/ATCC 细胞系的生长。对于四种化合物，在 MTT 测定中计算的三种测试细胞系的 IC _{50平均值约为 45 μM。}QSAR 允许为 HeLa 细胞系找到具有统计学意义的 OPLS 模型。体外代谢稳定性研究表明有利和不利的结构元素。代谢稳定性好，t _1/2超过 40 分钟，观察到三种衍生物，连同它们的抗增殖活性和良好的 ADMET 谱，使它们成为进一步研究的良好领先结构。

图形概要