Synthesis and biological evaluation of novel imidazo[1,2-a]pyridine-oxadiazole hybrids as anti-proliferative agents: Study of microtubule polymerization inhibition and DNA binding.
Sigalapalli DK, Kiranmai G, Parimala Devi G, Tokala R, Sana S, Tripura C, Jadhav GS, Kadagathur M, Shankaraiah N, Nagesh N, Babu BN, Tangellamudi ND.
Efforts towards the development of potential anticancer agents, a new series of imidazo[1,2-a]pyridine-oxadiazole hybrids were synthesized and evaluated for their in vitro anticancer activity against lung cancer (A549) and prostate cancer (PC-3, DU-145) cell lines. Amongst the compounds tested, 6d showed the highest potency on A549 cells with an IC<sub>50</sub> value of 2.8 ± 0.02 μM. Flow cytometric analysis of compound 6d treated A549 cells showed apoptosis induction by annexin-v/PI dual staining assay and the effect of 6d on different phases of cell cycle was also analyzed. Target based studies demonstrated the inhibition of tubulin polymerization by 6d at an IC<sub>50</sub> value of 3.45 ± 0.51 μM and its effective binding with CT-DNA. Further, the molecular modelling studies revealed that 6d has a prominent binding affinity towards α/β-tubulin receptor with admirable physico-chemical properties.