Inhibition of the Hsp90 function is an essential therapeutic approach and several
inhibitors were designed as anti-cancer agents. These inhibitors are ATPases and they aim to
deregulate Hsp90 folding function. ATPase proteins are common in human metabolism but they
form nonspecific targets. Hsp90 functions as dimer with coordinating chaperones. Heat Shock
Organizing Protein (Hop) forms a bridge between Hsp90 and Hsp70-Hsp40 complex to form Hsp90-Hsp70 coordination. Perturbing
conformational changes of these Hsp proteins, dimer formation, and protein-protein interactions inhibit Hsp90 substrate protein folding
function. This approach does not target all ATPase proteins but targets Hsp90 function solely. For this purpose, we designed compounds
to block Hsp90 function. Moreover, molecular docking studies as well as competition analysis of the compounds were performed with
Hsp90. Novel thiazolyl coumarine compounds were determined as valuable C-terminal Hsp90 inhibitors and provide promising templates
for the drug design. Anticancer activities of these novel compounds were tested by employing human colon (DLD-1) and liver cancer
(HepG2) cell lines. Thiazolyl coumarine compounds are found to be significant and useful for the treatment of human colon and liver
cancer as evidenced by in vitro and in silico results.
Keywords: Colon cancer, coumarine, heat shock protein 90, liver cancer, thiazole.
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