Synthesis and biological evaluation of 2-arylbenzimidazoles targeting Leishmania donovani

Synthesis of carboxyimidamide-substituted benzo[c][1,2,5]oxadiazoles and their analogs, and evaluation of biological activity against Leishmania donovani

“…The developed synthesis route to carboxyimidamide-substituted benzo[c] [1,2,5]oxadiazoles and related derivatives facilitates access to a compound library and determination of the structure-activity relationships for this antileishmanial heterocyclic chemotype. Carboxyimidamidesubstituted benzoxadiazole derivative 14 is the most promising compound of this study, demonstrating good antileishmanial inhibition activity in infected macrophages and, remarkably, no signs of cytotoxicity.…”

“…Initially, benzo[c] [1,2,5] The reaction of the obtained primary amide 3 with trifluoroacetic anhydride and Et 3 N in THF 9 gave the corresponding nitrile 4, which was converted to the amidoxime 5 by using hydroxylamine hydrochloride 10 in the presence of Et 3 N in EtOH. The final step to obtain the derivatives (6-18, 24) was carried out in the presence of the substituted phenyl isocyanates in THF or CHCl 3 .…”

“…The major issues to be confronted in Leishmania treatment are the toxicity of primary medicines and the development of parasite resistance. [1,2,5]oxadiazole derivatives showed activity against the intracellular Gram-negative bacterium Chlamydia pneumoniae. 4 In that study, a similarity-based model of C. pneumoniae dimethyladenosine transferase was used to virtually screen compounds from commercially available databases against C. pneumoniae.…”

“…The 2-arylbenzimidazoles found were then tested and proven active against L. donovani. 5 This prompted us to consider benzo[c] [1,2,5]oxadiazolederived compounds as a new family of antileishmanial agents. In addition, benzoxadiazoles and their N-oxides have been previously studied as antibiotic and antiparasitic agents.…”

“…In addition, benzoxadiazoles and their N-oxides have been previously studied as antibiotic and antiparasitic agents. 6 In this study, a facile synthesis route to carboxyimidamide-substituted benzoxadiazoles was developed, a set of 25 benzo[c] [1,2,5]oxadiazole derivatives and other structurally related compounds was synthesized and evaluated as antileishmanial agents.…”