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

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

AIELLO, Francesca;GAROFALO, Antonio
2009

Abstract

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
quinoxalinhydrazide,; anticancer activity,; apoptosis, novel agents
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/20.500.11770/150564
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