Inhibitors of apoptosis in testicular germ cells: Synthesis and biological evaluation of some novel IBTs bearing sulfonamide moiety

Pifithrin-α, a known p53 inactivator, inhibits p53-dependant mitochondrial cell death induced by toxins or γ-radiation. It has been found that aromatic IBT analogues of PFT-α are more cytoprotective and nonpeptide-based, isatin sulfonamides selectively inhibit caspases 3 and 7, responsible for mitochondrial mediated apoptosis. Therefore, we envisioned the synthesis of novel IBTs 4 and 5 bearing sulfonamide moiety and observed the mitigating effects of these IBTs in rescue of malathion induced apoptosis in testicular germ cells of goat. Two IBTs (4b; R = CH3, 5b; R1 = Cl) showed very high survival rate of cells whereas IBT 4f (R = NO2) showed some exceptional behaviour by increasing the apoptosis. These IBTs nullify the cytotoxic effect of malathion on mitochondria, following p53-independent pathway. Newly synthesized imidazo[2,1-b]benzothiazoles bearing sulfonamide moiety were tested as inhibitors of apoptosis, induced by malathion in testicular germ cells which showed promising anti-apoptotic activity. [Display omitted] ► Design and synthesis of scaffold bearing IBT and sulfonamide together. ► Evaluation of novel IBTs towards mitochondrial mediated inhibition of apoptosis. ► Two compounds showing very high survival rate of cells. ► These IBTs nullifying the cytotoxic effect of malathion on mitochondria following p53-independant pathway.