Synthesis and anti-leishmanial activity of 5-(5-nitrofuran-2-yl)-1,3,4-thiadiazol-2-amines containing N-[(1-benzyl-1H-1,2,3-triazol-4-yl)methyl] moieties

A novel series of 5-(5-nitrofuran-2-yl)-1,3,4-thiadiazol-2-amines were synthesized by introducing N-[(1-benzyl-1H-1,2,3-triazol-4-yl)methyl] moiety as a new functionality on the C-2 amine of thiadiazole ring via click chemistry. The title compounds namely, N-[(1-benzyl-1H-1,2,3-triazol-4-yl)methyl]-5-(5-nitrofuran-2-yl)-1,3,4-thiadiazol-2-amines (3a–n) were characterized by IR, NMR and MS spectra. These compounds were evaluated for their in vitro anti-leishmanial activity against promostigote form of the Leishmania major. Most compounds exhibited good anti-leishmanial activity against the promastigote form of L. major. The most active compound against promostigotes was found to be 4-methylbenzyl analog 3i, which significantly decreases the number of intracellular amastigotes per macrophage, percentage of macrophage infectivity and infectivity index.

Graphical abstractA series of N-[(1-benzyl-1H-1,2,3-triazol-4-yl)methyl]-5-(5-nitrofuran-2-yl)-1,3,4-thiadiazol-2-amines (3a–n) were synthesized and evaluated for their in vitro anti-leishmanial activity against Leishmania major.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► A novel series of 5-(5-nitrofuran-2-yl)-1,3,4-thiadiazol-2-amines were synthesized. ► N-[(1-benzyl-1H-1,2,3-triazol-4-yl)methyl] moiety was introduced as new pendent group. ► Most compounds showed good activity against promostigotes of Leishmania major. ► The most active compound was found to be 4-methylbenzyl analog 3i. ► Some compounds were found to be effective in reduction of intracellular amastigotes.