Discovery of a novel quinoxalinhydrazide with a broad-spectrum anticancer activity

Previously, we discovered a novel class of salicylhydrazidecompounds with remarkable activity in hormone-dependent and-independent human cancer cells. We then designed and synthesizednumerous analogues. Among these analogues, a quinoxalinhydrazidecompound, SC144, exhibited desirable physicochemical and druglikeproperties and therefore, was selected for further preclinicalinvestigation. In the present study, we evaluated the in vitro activityof SC144 in a range of drug-sensitive and -resistant cancer cell linesas well as its in vivo efficacy in MDA-MB-435 and HT29 micexenograft models. The broad-spectrum cytotoxicity of SC144 isespecially highlighted by its potency in ovarian cancer cells resistantto cisplatin, breast-cancer cells resistant to doxorubicin, and coloncancer cells resistant to oxaliplatin. Furthermore, its activity wasindependent of p53, HER-2, estrogen and androgen receptor expressions.We also examined the effect of SC144 on cell cycle progressionand apoptosis in select cell lines. Considering its cytotoxicity profilein a variety of in vitro and in vivo cancer models as well as its effectson cell cycle regulation and apoptosis, SC144 appears to represent apromising agent for further clinical development