The present work mainly aims to discover novel small molecular inhibitors against important molecular target T3151 Abl mutant involved in leukemia. Five heterocyclic compounds 1-5 with N and S atoms (thiosemicarbazone, thiadiazole and thiazolidinoyl derivatives) were synthesised and characterised using spectral data. Docking study was carried out for 1-5 against the T315I Bcr-Abl mutant. The compounds 3-5 with phenothiazine pharmacophore showed promising docking score than with the derivatives having the coumarin pharmacophore 1 and 2. So the compounds 3-5 were tested for their anticancer activity against leukemic K562 cell line by trypan blue, MTT and LDH assays. Compound 5 showed marked anticancer activity and exhibited an IC50 value of 11.12 and 30.80 µg/ml against trypan blue and MTT assay respectively. Further a dose-dependent increase in LDH release was observed, confirming the antiproliferative potential of the compounds.
Key words: Chronic myelogenous leukemia, thiadiazole, synthesis, characterisation, molecular docking, antiproliferative activity.
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