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In the present study an efficient strategy for the synthesis of thiazole and thiadiazole derivatives was developed and clubbed together both of the substituted nucleus to form the analogues of combretastatin A-4 (tubulin polymerization inhibitors.). Synthesis was started by the reaction of substituted benzoic acid with thionyl chloride followed by the reaction with hydrazine, p-chloro benzaldehyde and thioglycolic acid to form substituted thiazole derivatives. On the other side hydrazides were reacted with ammonium thiocyanate and strong acid to form substituted thiadiazole compounds. Finally thiazole and thiadiazole compounds were clubbed with the help of dioxan and triethylamine. All novel derivatives (TH01-TH40) were screened for their cytotoxicity activity using MTT assay against three cancer cell lines viz. A-549 (lung carcinoma), HT-29 (colon carcinoma), HeLa (cervix carcinoma). Compounds TH08 exhibited highest activity, due to the presence of trimethoxy substitution on phenyl ring. In QSAR study these results were correlated with physicochemical parameters and the correlation of XlogP, kaapa2, Quadrupole1 with cytotoxic activity on A-549 (lung carcinoma) was found highest (r2: 0.941; F: 99.103; Se: 0.0006). In docking study binding of active molecule (TH08) was found very well with α, β tubulin (PDB: 1SA0) protein.

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Myocardial Infarction is the leading cause of death and disability worldwide. It has been reported that GCN-5 inhibitors inhibit GCN-5 mediated acetylation of PGC-1 alpha, which in turns enhances PGC-1alpha activity, mitochondrial function and oxidative metabolism. PGC-1α activity is regulated by Histone deacetylases and Histone acetyl transferases. In particularly PGC-1α is directly acetylated by HAT enzyme-general control non derepressible 5 (GCN-5). Ethyl-2-methylquinoline-3-carboxylate is reported to be a specific inhibitor of GCN-5. PGC-1 α levels are reported to be reduced in heart following myocardial infarction and up regulation of PGC-1 α confers protection against ischaemia and reperfusion in cardiomyoblast cells. Thus, in present study we investigated the protective effect of Ethyl-2-methyl quinoline-3-carboxylate as GCN-5 inhibitor in modulation of PGC-1 alpha activity during ischemia and reperfusion induced myocardial injury.