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.
Keywords: Thiazole, Combretastatin A-4, Thiadiazole, Cytotoxicity, QSAR, MTT, Docking.
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