Synthesis and preliminary in vitro activity of mono- and bis-1H-1,2,3-triazole-tethered β-lactam–isatin conjugates against the human protozoal pathogen Trichomonas vaginalis

In this study, we describe the synthesis of mono- and bis-1H-1,2,3-triazole-tethered β-lactam–isatin conjugates using copper-catalysed azide-alkyne cycloaddition reaction between mono- and di-propargylated azetidin-2-ones and N-alkylazido isatins. The synthesized conjugates were evaluated for their preliminary in vitro analysis against Trichomonas vaginalis at 50 μM. The efficacy of synthesized hybrids was observed to depend on the substituent at N-1 position of β-lactam ring, as well as the presence of single/double 1H-1,2,3-triazole linker. Among the synthesized conjugates, the presence of a p-tolyl substituent at N-1 of β-lactam ring was preferred for good activity profiles while the increase in spacer length did not influence the efficacy of the compounds. Compounds with high levels of potency were further analysed to determine their IC(50) values, as well as cytotoxicity profiles against mammalian cells. The most active compound in the synthesized conjugates displayed an IC(50) value of 10.49 μM against cultured G3 strain of T. vaginalis and was non-toxic to cultured mammalian HeLa cells at the same concentration. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00044-014-0956-6) contains supplementary material, which is available to authorized users.