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

• Published in: Medicinal chemistry research Vol. 32; no. 4; pp. 705 - 712
• Main Authors: Zhao, Shijia, Zhang, Xiaoyan, Tang, Min, Liu, Xiaocheng, Deng, Jialun, Zhou, Wei, Xu, Zhi
• Format: Journal Article
• Language: English
• Published: New York Springer US 2023; Springer Nature B.V
• Subjects: Biochemistry; Biomedical and Life Sciences; Biomedicine; Bioorganic Chemistry; Breast cancer; Cytotoxicity; Dihydroartemisinin; Hybrids; Inorganic Chemistry; Medicinal Chemistry; Original Research; Pharmacology/Toxicology; Selectivity; Toxicity; Tumor cell lines; breast cancer; hybrid molecules; drug resistance; dihydroartemisinin; isatin
• ISSN: 1054-2523; 1554-8120
• DOI: 10.1007/s00044-023-03030-0

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 (IC 50 : 1.27 µM) was 14.88 -> 78.74 times more active than adriamycin (IC 50 : 18.90 µM), DHA (IC 50 : 28.28 µM) and ART (IC 50 : > 100 µM) against MCF-7 breast cancer cells, whereas hybrid 5c (IC 50 : 2.39 and 3.95 µM) was superior to adriamycin (IC 50 : 3.38 and >100 µM), DHA (IC 50 : 48.80 and 82.78 µM) and ART (IC 50 : >100 and >100 µM) against MDA-MB-231 and MDA-MB-231/ADR breast cancer cell lines. Moreover, the selected hybrids (IC 50 : >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.