Design, Synthesis and Biological Evaluation of Morpholinated Isatin-Quinoline Hybrids as Potential Anti-Breast Cancer Agents.

Abstract Keeping in view the emerging need of potent and safer anti-breast cancer agents as well as pharmacological attributes of isatin, quinoline and morpholine derivatives, novel hydrazone linked morpholinated isatin-quinoline hybrids has been designed, synthesized and evaluated as anti-breast cancer agents. Synthesized hybrid compounds were preliminary 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 inactive against hormone negative MDA-MB-231 cells. Potent compounds were further evaluated against L929 (noncancerous skin fibroblast) cell line and found highly selective for MCF-7 cells over L929 cells. Cell cycle analysis confirmed that most potent compound AS-4 (MCF-7: GI50 = 4.36 µM) cause mitotic arrest at G2/M-phase. Due to higher selectivity toward estrogen receptor alpha (ERα) dependent MCF-7 cells various binding interactions of AS-4 with ERα are also streamlined, suggesting the capability of AS-4 in completely blocking ERα. Overall study suggest that, AS-4 can act as a potential lead for further development of potent and safer anti-breast cancer agents.