A series of new triazolo linked 4β-amidopodophyllotoxin conjugates () were synthesized using click chemistry and evaluated for their antitumor activity against four human cancer cell lines. Among them, two compounds ( and ) showed significant anticancer activity with IC values of 0.9 and 0.07 μM, respectively. Biological studies are conducted into the cell-cycle distribution of these conjugates inducing G2/M-phase arrest, apart from an increase in the levels of caspase-3 proteins, followed by apoptotic cell death. A tubulin polymerization assay analysis showed that these compounds effectively inhibit microtubule assembly in HeLa cells and, moreover, Hoechst 33258 and Immunohistochemistry staining suggest that these compounds induce cell death by apoptosis. The docking studies showed that compounds and interact and bind efficiently with the tubulin protein at the colchicine site.
A library of imidazopyridine-propenone conjugates () were synthesized and evaluated for their antitumor activity against four human cancer cell lines, namely, prostate (DU-145), lung (A549), cervical (Hela) and breast (MCF-7) cancer cell lines. These conjugates showed good to moderate activity against the tested cell lines. Among them, two conjugates ( and ) showed significant antiproliferative activity against the human lung cancer cell line (A549) with IC values of 0.86 μM and 0.93 μM, respectively. Flow cytometry analysis revealed that these compounds arrested the cell cycle at the G/M phase in the human lung cancer cell line (A549), inhibiting tubulin polymerization leading to apoptosis. Further, Hoechst staining, decrease in mitochondrial membrane potential and Annexin V-FITC assay suggested that the cell death was due to apoptosis induction. Overall, the present investigation demonstrated that the synthesized imidazopyridine-propenone conjugates are promising tubulin inhibitors and apoptotic inducers.
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