Synthesis of N-2-aryl-substituted-1,2,3-triazole Derivatives as Novel Inhibitors of Entamoeba histolytica

Abstract

Approximately one tenth of the world population is believed to be infected with Entamoeba histolytica, with 100,000 deaths worldwide each year due to invasive amebiasis in the developing countries. Thus new effective agents with less toxicity against amoebiasis are urgently required. As part of our ongoing search for novel bioactive molecules, chalcone (1a-e) based 1,2,3-triazole derivatives (2a-j) were synthesized and evaluated for their in vitro antiamoebic activity. In this study an efficient one pot three-component stepwise approach using azide-chalcone oxidative cycloaddition and post-triazole arylation has been followed to get new N-2-aryl-substituted-1,2,3-triazole derivatives (2a-j) under mild conditions with moderate yields. The structures of all the compounds were established on the basis of FT-IR, 1 H-NMR, 13 C-NMR and Mass spectral analyses. The in vitro antiamoebic activity was evaluated using HM1:IMSS strain of E. histolytica and their IC50 values were calculated. The results showed that the title compounds possess comparable to potent inhibitory effect against E. histolytica trophozoites than the current drug, metronidazole. The toxicity profile of all the compounds was also checked by hemolytic assay and the results showed that chalcones 1b, 1e and 1,2,3-triazoles (2a-2e), (2g-2j) have lesser toxicity at 100 µg/ml concentration than the ref- erence drugs fluconazole and metronidazole. The study suggests that these compounds may further be explored for the devel- opment of new leads for amoebiasis.