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

ABSTRACT: 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.

SUBMITTER: Zhao S 

PROVIDER: S-EPMC9926453 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature