Nitroimidazolyl-1,3,4-thiadiazole-based anti-leishmanial agents: Synthesis and in vitro biological evaluation

A series of 1-[5-(1-methyl-5-nitro-1H-imidazol-2-yl)-1,3,4-thiadiazol-2-yl]-4-aroylpiperazines were synthesized and evaluated in vitro against Leishmania major. Most of the target compounds exhibited good anti-leishmanial activity against the promastigote form of L. major at non-cytotoxic concentrations. The most active compound was 1-[(5-chloro-2-thienyl)carbonyl]-4-[5-(1-methyl-5-nitro-1H-imidazol-2-yl)1,3,4-thiadiazol-2-y]piperazine (5f) with an IC50 value of 9.35 +/- 0.67 mu M against L. major promastigotes. In addition, this compound was effective against intracellular L. major and significantly decreased the infectivity index. (c) 2008 Elsevier Masson SAS. All fights reserved.