A Novel Approach to Inhibit Heat Shock Response as Anticancer Strategy by Coumarine Compounds Containing Thiazole Skeleton

Abstract

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.

Enamines and Dimethylamino Imines as Building Blocks in Heterocyclic Synthesis: Reactions of DMF‐DMA Reagent with Different Functional Groups

“…The mixture of compound 359 and ethyl 4‐chloro‐3‐oxobutanoate ( 360 ) reagent was refluxed in acetonitrile for 2 hours to synthesize thiazolyl‐β‐ketoester compounds ( 361 ). The importance of synthesis of thiazole compounds from enamines was especially emphasized for the chemistry of heterocyclic compounds by Koca et al [84,85] . (Scheme 47).…”

Kurkumin’in Osteosarkomada Doğal RANKL İnhibitörü Olarak Biyolojik Değerlendirilmesi

“…To measure cell viability, XTT cell proliferation kit was applied according to instructions from the supplier. The IC 50 value of curcumin on Saos-2 cells was calculated with GraphPad Prism 6.0 software [12,13].…”

One-pot and multi-step syntheses of new 2-(4,5-dihydro-1H-pyrazol-1-yl) thiazole derivatives

“…Accordingly, the compounds A are analogous to a certain thiourea derivative compounds. In a previous work 28 , thiazolyl-β-ketoester compounds were synthesized by a two step reaction using thiourea derivatives by our group. In this work, pyrazole and thiazole scaffolds were integrated by this method we described earlier.…”