Background: A new series of 1,2,3-triazol-nitrostyrene derivatives was designed, synthesized, and evaluated for cytotoxic activity against Hep-2 and L929 cell lines.

Methods: The synthetic procedure started from the functionalization of 4-hydroxybenzaldehyde with propargyl bromide and a subsequent click reaction to give 1,2,3-triazole derivatives. Then, the reaction of the mentioned derivatives with nitromethane led to the formation of the title compounds in excellent yields.

Results: Most of the compounds exhibited better cytotoxic activity with respect to the standard drug 5-fluorouracil. Among them, (E)-1-(3,4-dichlorobenzyl)-4-((4-(2-nitrovinyl)phenoxy)methyl)-1H- 1,2,3-triazole 6i (IC50 = 4.66 ± 1.3 μM) against the Hep-2 cell line and (E)-1-(2,3-dichlorobenzoyl)- 4-((4-(2-nitrovinyl)phenoxy)methyl)-1H-1,2,3-triazole 6g (IC50 = 5.18 ± 0.8 μM) against the L929 cell line exhibited the best cytotoxic effects.

Conclusion: Moreover, the acridine orange/ethidium bromide double staining technique showed that the most potent compounds 6i and 6g could induce apoptosis in studied cancer cell lines.