The novel coumarin[3,2-c]thiophene and its hydroxamic acid and ureido derivatives: synthesis and cytostatic activity evaluations

摘要

In the present paper, we report on the synthesis and in vitro antitumour effects of novel hydroxamic acid (compounds 4 and 5) and ureido (compounds 7-11) derivatives containing coumarin[3,2-c]thiophene moiety. The results of antiproliferative assays performed on a panel of selected human tumour cell lines revealed stronger concentration-dependent antiproliferative activity of coumarin[3,2-c]thiophene (7-11) ureido derivatives in comparison with coumarin[3,2-c]thiophene hydroxamic acid derivatives (4 and 5). Nevertheless, compounds 7-10 were cytotoxic on normal human fibroblasts as well. Importantly, the ureido derivative 11 and hydroxamic acid derivatives 4 and 5 showed pronounced and selective inhibitory activity towards cervical carcinoma (HeLa) cell line with concomitant low or no cytotoxicity on normal human fibroblasts. These compounds can therefore be considered as potential antitumour lead compounds for further structural optimization.