Green synthesis, antileishmanial activity evaluation, and in silico studies of new amino acid-coupled 1,2,4-triazoles

Abstract

Candidates of triazole-containing amino acid derivatives 5a−k were prepared under green chemistry conditions via multicomponent reaction using lemon juice as an acidic catalyst. All compounds were characterized by different spectral and elemental analyses. They were evaluated for their in vitro antileishmanial activity against miltefosine and amphotericin B deoxycholate as reference drugs. Compounds 5c, 5d, 5e and 5f showed superior potencies to miltefosine by 200 folds. These compounds are well tolerated by experimental animals orally up to 250 mg/kg and parenterally up to 100 mg/kg. Reverse docking approach against validated leishmanial targets pinpointed mitogen-activated protein kinase (MAPK) as a possible putative antileishmanial target. In addition, in silico predictions revealed that these compounds exhibited promising drug-likeness and pharmacokinetics profile.