Synthesis of imidazothiadiazole-benzimidazole conjugates as mitochondrial apoptosis inducersElectronic supplementary information (ESI) available: Experimental procedures, spectral data of all the final compounds. See DOI: 10.1039/c4md00219a

A series of imidazothiadiazole-benzimidazole conjugates ( 3a-z ) were synthesized and evaluated for their cytotoxic activity against a set of four selected human cancer cell lines. Amongst them, compounds 3b and 3y exhibited significant antiproliferative activity in ME-180 (cervical) cell line. Flow cytometric analysis showed that these two compounds arrested the cell cycle in the G 0 /G 1 phase leading to the loss of mitochondrial membrane potential followed by apoptotic cell death. Further, Hoechst 33258 staining, DNA fragmentation assay, Annexin V staining assay and caspase-3 also suggested that 3b and 3y induced cell death by apoptosis. Docking studies revealed that compound 3b binds to the Gly142, Phe101, Asn140 and Arg143 on B-cell lymphoma 2 (Bcl-2) proteins and inhibition of Bcl-2 protein could be the possible mechanism of action for these compounds. A series of imidazothiadiazole-benzimidazole conjugates ( 3a-z ) were synthesized and evaluated for their cytotoxic activity against a set of four selected human cancer cell lines. Compounds 3b and 3y exhibited significant antiproliferative activity against the ME-180 (cervical) cell line.