Synthesis and cytotoxic activity on human cancer cells of carbamate derivatives of 4β-(1,2,3-triazol-1-yl)podophyllotoxin

Carbamate derivatives of 4β-(1,2,3-triazol-1-yl)podophyllotoxin were synthesized by means of click chemistry, and their cytotoxicities against human cancer cell lines HL-60, A-549, HeLa, and HCT-8 were evaluated. Some compounds were more potent than the anticancer drug etoposide. 4′-O-Demethyl-4β-[(4-hydroxymethyl)-1,2,3-triazol-1-yl]-4-deoxypodophyllotoxin cyclopentyl carbamate, the most potent compound, induced cell cycle arrest in the G2/M phase accompanied by apoptosis in A-549 cells. Furthermore, this compound inhibited the formation of microtubules in A-549 cells and caused the inhibition of DNA topoisomerase-II. Carbamate derivatives of 4β-(1,2,3-triazol-1-yl)podophyllotoxin exhibited promising in vitro cytotoxicities. Compound 22 induced cell cycle arrest in the G2/M phase accompanied by apoptosis in A-549 cells, and inhibited the formation of microtubules and DNA topoisomerase-II. [Display omitted] •Eleven carbamates of 4β-(1,2,3-triazol-1-yl)podophyllotoxin were synthesized by click chemistry.•Some carbamates exhibited potent cytotoxic activity compared with VP-16.•Compound 22 arrests cell cycle in the G2/M phase accompanied by apoptosis in A-549 cells.•Compound 22 inhibits the formation of microtubules in A-549 cells.•Compound 22 inhibits DNA topoisomerase-II.