Acyl Thiourea Derivatives Containing Pyrazole Ring Selective Targeting of Human Aurora Kinases in Breast and Bone Cancer

Abstract

Several oncogenic pathways may lead to cancer. Pharmaceutical research develops efficacious compounds to inhibit these pathways. Current inhibitor drugs may block several pathways simultaneously but cause adverse and side effects. Therefore, we designed novel acyl thiourea derivatives containing pyrazole ring to selectively inhibit a kinase dependent pathway in cancer. In this study, breast and bone cancer cells were employed to monitor this selectivity. Since metastatic breast cancer spreads to bone, MCF-7 along with epithelial (Saos-2) and fibroblast (MG-63) human bone cancer cell lines were used to observe inhibitory effects of the synthesized compounds. It has been reported that Estrogen receptor alpha (ER-alpha) and Aurora kinase A and B are involved in different pathways at breast and bone cancer mechanism. Synthesized novel inhibitors presented in this work effectively and selectively bind to Aurora kinase A and B but do not interact with ER-alpha however; a generic inhibitor PHA-739358 binds to all three enzymes. This improved binding mode of the novel inhibitors may be a useful therapeutic strategy for the treatment of breast and bone cancer approaches and provides potency to personalized medicine.