Design, synthesis and cytotoxic activity of sulfonylated derivatives of camptothecin.

With the intention of advancing our research on diverse C-20 derivatives of camptothecin (CPT), CPT derivatives bearing sulphonamide and sulfonylurea chemical scaffolds and different substituent groups have been designed, synthesised and evaluated for cytotoxicity against four tumour cell lines, A-549 (lung carcinoma), KB (nasopharyngeal carcinoma), MDA-MB-231 (triple-negative breast cancer) and KBvin (an MDR KB subiline). As a result, all the synthesised compounds showed promising cytotoxic activity against the four cancer cell lines tested, and were more potent than irinotecan. Importantly, compounds , , and possessed better antiproliferative activity against all tested tumour cell lines with IC values of 0.0118 - 0.5478 μM, and resulted approximately to times more cytotoxic than topotecan against multidrug-resistant KBvin subline. Convincing evidences are achieved that incorporation of sulphonamide and sulfonylurea motifs into position-20 of camptothecin confers markedly enhanced cytotoxic activity against cancer cell lines.