Quinoline-Proline, Triazole Hybrids: Design, Synthesis, Antituberculosis, Molecular Docking, and ADMET Studies

A series of novel quinoline-proline hybrids (11a-g) and quinoline-proline-1,2,3-triazole hybrids (12-14) were synthesized by click chemistry based on molecular hybridization concept and were characterized by NMR, mass spectrometry, and elemental analysis. All the titled target compounds were tested for antitubercular activity by MABA and LORA methods by in vitro. Interestingly, two compounds (2R,4S)-1-((2-cyclopropyl-4-(4-fluorophenyl)-quinolin-3-yl)-methyl)-4-(4-nitrobenzamido)-N-phenylpyrrolidine-2-carboxamide (11b) and (2R,4S)-1-((2-cyclopropyl-4-(4-fluorophenyl)-quinolin-3-yl)-methyl)-4-(4-fluorobenzamido)-N-phenylpyrrolidine-2-carboxamide (11c) exhibited significant activity against the tested Mycobacterium tuberculosis H37Rv strain. Further, the cytotoxicity (CC50) profile of the titled compounds against the Vero cell was performed and discussed. A molecular docking study of the hit compounds (11b and 11c) was also performed to find their putative binding interaction with the active site of the target proteins. Finally, in silico ADMET properties were also predicted for all the synthesized molecules to evaluate their drug-likeness behavior.