Design, synthesis and anti-breast cancer properties of butyric ester tethered dihydroartemisinin-isatin hybrids.

Fifteen novel butyric ester tethered dihydroartemisinin-isatin hybrids 4a-d and 5a-k were designed, synthesized, and evaluated for cytotoxicity against four human breast cancer cell lines, including MCF-7, MDA-MB-231, MCF-7/ADR and MDA-MB-231/ADR using the MTT method. A significant part of them were active against the four tested cancer cell lines, and the representative hybrid 5b (IC50: 1.27 µM) was 14.88 -> 78.74 times more active than adriamycin (IC50: 18.90 µM), DHA (IC50: 28.28 µM) and ART (IC50: > 100 µM) against MCF-7 breast cancer cells, whereas hybrid 5c (IC50: 2.39 and 3.95 µM) was superior to adriamycin (IC50: 3.38 and >100 µM), DHA (IC50: 48.80 and 82.78 µM) and ART (IC50: >100 and >100 µM) against MDA-MB-231 and MDA-MB-231/ADR breast cancer cell lines. Moreover, the selected hybrids (IC50: >100 µM) displayed non-cytotoxicity towards normal MCF-10A breast cells, and the SI values of hybrids 5b,c were >78.74 and >41.84 respectively, demonstrating their excellent selectivity and safety profiles. Accordingly, hybrids 5b,c could serve as promising anti-breast cancer candidates and deserved further preclinical evaluations.