Design, synthesis, and biological evaluation of novel morpholinated isatin-quinoline hybrids as potent anti-breast cancer agents

Keeping in view the emerging need for potent and safer anti-breast cancer agents as well as the pharmacological attributes of isatin, quinolone, and morpholine derivatives, novel hydrazine-linked morpholinated isatin-quinoline hybrids were designed, synthesized, and evaluated as anti-breast cancer agents. The synthesized hybrid compounds were preliminarily screened against two breast cancer cell lines (MCF-7 and MDA-MB-231). Almost all synthetics showed potent inhibitory potential against hormone-positive MCF-7 cells while being inactive against hormone-negative MDA-MB-231 cells. Potent compounds were further evaluated against the L929 (noncancerous skin fibroblast) cell line and found to be highly selective for MCF-7 cells over L929 cells. Cell cycle analysis confirmed that the most potent compound AS-4 (MCF-7: GI(50) = 4.36 mu M) causes mitotic arrest at the G(2)/M phase. Due to higher selectivity toward estrogen receptor alpha (ER alpha)-dependent MCF-7 cells, various binding interactions of AS-4 with ER alpha are also streamlined, suggesting the capability of AS-4 to completely block ER alpha. Overall, the study suggests that AS-4 can act as a potential lead for further development of potent and safer anti-breast cancer agents.

Automated summary

Novel hydrazine-linked morpholinated isatin-quinoline hybrids were designed, synthesized, and evaluated as potent and safer anti-breast cancer agents, showing high inhibitory potential against hormone-positive breast cancer cells with selective action and mitotic arrest at the G(2)/M phase, suggesting AS-4 as a potential lead compound for further development.