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

AbstractFifteen novel butyric ester tethered dihydroartemisinin-isatin hybrids4a-d and5a-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 hybrid5b (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 hybrid5c (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 hybrids5b,c were>78.74 and>41.84 respectively, demonstrating their excellent selectivity and safety profiles. Accordingly, hybrids5b,c could serve as promising anti-breast cancer candidates and deserved further preclinical evaluations.
Source: Medicinal Chemistry Research - Category: Chemistry Source Type: research