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), <b>38</b> CPT derivatives bearing sulphonamide and sulfonylurea chemical scaffolds and different substituent groups have been designed, synthesised and evaluated <i>in vitro</i> 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 <i>in vitro</i> cytotoxic activity against the four cancer cell lines tested, and were more potent than irinotecan. Importantly, compounds <b>12b</b>, <b>12f</b>, <b>12j</b> and <b>13 l</b> possessed better antiproliferative activity against all tested tumour cell lines with IC₅₀ values of 0.0118 − 0.5478 μM, and resulted approximately <b>3</b> to <b>4</b> 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.