Synthesis of new pyrazole-triazole hybrids by click reaction using a green solvent and evaluation of their antitubercular and antibacterial activity

Abstract

A new series of pyrazole-based 1,2,3-triazole derivatives (6a-x) were synthesized by employing click reaction using a 2:1 mixture of PEG-400 and water as green solvent. The synthesized intermediate and final compounds were characterized by 1H NMR, 13C NMR, and mass spectra and elemental analysis techniques. The structure of one of the final compounds, 6a was evidenced by single crystal X-ray diffraction study. Among the twenty-four compounds, five compounds (6a, 6b, 6d, 6f, and 6g) showed significant antitubercular activity against Mycobacterium tuberculosis H<inf>37</inf>Rv with a minimum inhibitory concentration (MIC) ? 6.25 ?g/mL. The 4-(((5-(4-Chlorophenyl)-1-phenyl-1H-pyrazol-3-yl)methoxy)methyl)-1-cyclohexyl-1H-1,2,3-triazole (6g) was the most potent compound of the series, which showed a MIC of 3.13 ?g/mL. The cytotoxicity study of active anti-TB compounds on normal Vero cells revealed that the compounds are non-toxic with a high selectivity index (>37). Most of the pyrazole-1,2,3-triazole derivatives with a 4-chlorophenyl substitution at position-5 of the pyrazole ring showed a better anti-TB activity than the corresponding 4-bromophenyl or 4-methoxyphenyl substituted derivatives. The target compounds were also evaluated for their in vitro antibacterial activity and six compounds (6a, 6c, 6d, 6e, 6l, and 6w) showed promising inhibition activity against four tested strains. © Springer Science+Business Media Dordrecht 2015.