3-Nitrotriazole-based piperazides as potent antitrypanosomal agents

European Journal of Medicinal Chemistry
Maria V PapadopoulouMarcel Kaiser

Abstract

Novel linear 3-nitro-1H-1,2,4-triazole-based piperazides were synthesized and evaluated as antitrypanosomal agents. In addition, some bisarylpiperazine-ethanones which were formed as by-products were also screened for antiparasitic activity. Most 3-nitrotriazole-based derivatives were potent and selective against Trypanosoma cruzi parasites, but only one displayed these desired properties against Trypanosoma brucei rhodesiense. Moreover, two 3-nitrotriazole-based chlorophenylpiperazides were moderately and selectively active against Leishmania donovani. Although the bisarylpiperazine-ethanones were active or moderately active against T. cruzi, none of them demonstrated an acceptable selectivity. In general, 3-nitrotriazole-based piperazides were less toxic to host L6 cells than the previously evaluated 3-nitrotriazole-based piperazines and seven of 13 were 1.54- to 31.2-fold more potent antichagasic agents than the reference drug benznidazole. Selected compounds showed good ADMET characteristics. One potent in vitro antichagasic compound (3) was tested in an acute murine model and demonstrated antichagasic activity after a 10-day treatment of 15 mg/kg/day. However, neither compound 3 nor benznidazole showed a statistically sign...Continue Reading

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Citations

Dec 25, 2015·European Journal of Medicinal Chemistry·Avninder S BhambraVladimir Krystof
Aug 23, 2016·Journal of Medicinal Chemistry·Stephanie RussellMatthew J Piggott
Mar 1, 2017·Antimicrobial Agents and Chemotherapy·Maria V PapadopoulouMaria Terezinha Bahia
Jun 12, 2019·International Journal of Molecular Sciences·Anacleto S de SouzaAdriano D Andricopulo
Jul 28, 2017·Current Medicinal Chemistry·Susimaire Pedersoli MantoaniIvone Carvalho
Apr 10, 2021·Journal of Experimental Pharmacology·Ana Lia MazzetiVanessa Carla Furtado Mosqueira
Jun 9, 2018·Journal of Medicinal Chemistry·Rubén Martín-EscolanoManuel Sánchez-Moreno

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