L-proline catalyzed ring transformation of 5-substituted tetrazole to 1,3,4-oxadiazoles as anti-tubercular agents

Abstract

An innovative class of novel 2-aryl-5-(1-aryl-1H-pyrazol-3-yl)-1,3,4-oxadiazoles 5i–w have been synthesized from ring transformation using L-proline as an organocatalyst. This novel method using organocatalyst is a splendid example of the green reaction with improved yields. The molecular docking analysis of compounds 5i–w were investigated with enoyl-acyl carrier protein reductase (InhA) enzyme (PDB ID: 4TZK) as anti-tubercular target molecules. The docking study implied that the synthesized compounds exhibited favorable binding modes and affinity. Further, the anti-tubercular activity was investigated against Mycobacterium tuberculosis (MTB) H₃₇Rv strain which demonstrated that the compounds 5i, 5j, 5k, and 5l exhibited excellent activity at the 6.25 µg/ml concentrations, whereas the compounds 5m, 5n, 5o, 5s, and 5w have shown the activity at 12.50 µg/ml concentration, respectively.

Graphical Abstract

Keywords:

• Anti-tubercular agents
• N-arylsydnone
• pyrazole
• 1,3,4-oxadiazole
• 1,3-dipolarcycloaddition

Acknowledgments

The authors pay heartfelt thanks to DST-SAIF and University Scientific Instrumentation Center (USIC), Karnataka University Dharwad, for providing spectral characterization and we also thank Central Research Laboratory, Maratha Mandal's NGH Institute of Dental Sciences and Research Centre, Belgaum India for carrying out Anti-tuberculosis (TB) activity. One of the authors (TVM) is grateful to DST-KSTePS, Government of Karnataka for providing the Research fellowship.