Heat Shock Protein 90 c-Terminal Inhibitors in Cancer Treatment

Coumarine (2H-1-benzopyran-2-ones) is benzopyrone class compounds and its derivatives are shown a wide spectrum of biological activity. Particularly, coumarine derivative compounds (novobiocin, coumermycin A1, KU135, and chlorobiocin) have an affinity for binding to the CTD and disrupting Hsp90 dimerization. Consequently, these compounds inhibit proper folding of oncogenic client proteins and cause elimination of the substrate proteins via ubiquitination-proteasome pathway [6,7]. In an effort, we designed and synthesized novel thiazolyl coumarine derivatives, and their anti-cancer activities were tested on human colon (DLD-1) and liver (HepG2) cancer cell lines. According to the biochemical and in-silico experiments, thiazolyl coumarine derivative compounds inhibited Hsp90 chaperone functions through disrupting CTD conformational change. Furthermore, these compounds disrupted interaction between Hsp90, Hop, Hsp40, and Hsp70 proteins in cancer cells. Briefly, thiazolyl coumarine derivatives are effective and potential Hsp90 CTD inhibitors as anti-cancer agents [6]. CTD inhibition strategy and increased biochemical and pharmacological knowledge about Hsp90 provide significant opportunities for anti-cancer drug development.