Synthesis and anti-protozoal activity of novel dihydropyrrolo[3,4-d][1,2,3]triazoles

1,2,4-Oxadiazole and 1,2,3-triazole containing heterocyclic compounds continue to gain interest in synthesis of chemical entities and exhibit various biological activities as anti-protozoal and anti-cancer agents. By using the principle of bioisosterism, a series of novel oxadiazolyl pyrrolo triazole diones; namely, (3aS,6aR)-1-((3-(4-substituted phenyl)-1,2,4-oxadiazol-5-yl)methyl)-5-phenyl-1,6a-dihydropyrrolo[3,4-d][1,2,3] triazole-4,6(3aH,5H)-diones (5a–k) was designed and synthesized by the 1,3-dipolar cycloaddition reaction of novel 5-azidomethyl 3-aryl substituted 1,2,4-oxadiazoles (4a–k) with N-phenyl maleimide. The structures of all the cycloadducts were elucidated by means of spectroscopic methods and physical characteristics. The in vitro anti-protozoal and cytotoxic activities of these novel heterocyclic compounds were investigated.

Graphical abstractA series of novel dihydropyrrolo[3,4-d][1,2,3]triazoles (5a–k) were designed and synthesized. The title compounds were assayed for their anti-protozoal activity against Trypanosoma brucei rhodesiense, Trypanosoma cruzi, Leishmania donovani, Plasmodium falciparum and cytotoxicity against L6 cells.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► A series of novel dihydropyrrolo[3,4-d][1,2,3]triazole derivatives were synthesized. ► They were evaluated for anti-protozoal and cytotoxic activities. ► Hammett correlations were established for chloromethyl and azidomethyl oxadiazoles.