Synthesis of 2-alkylthio-N-(quinazolin-2-yl)benzenesulfonamide derivatives: anticancer activity, QSAR studies, and metabolic stability

Jarosław Sławiński,Mariusz Belka,Tomasz Bączek,Anna Kawiak,Aneta Pogorzelska,Krzysztof Szafrański,Beata Żołnowska

doi:10.1007/s00706-018-2251-6

Jarosław Sławiński, Mariusz Belka + Show 5 more

Open Access

https://doi.org/10.1007/s00706-018-2251-6

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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 t1/2 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

Highlights

Cancer diseases are the second leading cause of death in developed countries and are expected to surpass heart diseases as the leading cause of death in the few years [1]
As presented in Scheme 1, the desired 2-alkylthio-N(quinazolin-2-yl)benzenesulfonamide derivatives 9–24 have been obtained by reacting the appropriate N-(2alkylthio-4-chloro-5-methylbenzenesulfonyl)cyanamide potassium salts 1–8 with 20-aminoacetophenone or 2-aminobenzophenone
We have developed methods for the synthesis of novel series of 2-alkylthio-N-(quinazolin-2-yl)benzenesulfonamide derivatives

Summary

Introduction

Cancer diseases are the second leading cause of death in developed countries and are expected to surpass heart diseases as the leading cause of death in the few years [1]. 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. Derivatives 12, 18, 22, and 24 displayed the most potent cytotoxic effects against all tested cell lines. As with MTT assays against HCT-116, HeLa and MCF-7, compounds 12, 18, 22, and 24 showed the strongest antiproliferative effect while derivatives 13, 14, 19, and 20 exhibited very weak cytotoxic activity.

Results

Conclusion