Abstract
A series of new triazolo linked 4β-amidopodophyllotoxin conjugates (
9a-l
) were synthesized using click chemistry and evaluated for their antitumor activity against four human cancer cell lines. Among them, two compounds (
9c
and
9j
) showed significant anticancer activity with IC
50
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
9c
and
9j
interact and bind efficiently with the tubulin protein at the colchicine site.
A series of new triazolo linked 4β-amidopodophyllotoxin conjugates (
9a-l
) were synthesized using click chemistry and evaluated for their antitumor activity.