Development of Novel Sulfonamide-Based Pyrazole-Clubbed Pyrazoline Derivatives: Synthesis, Biological Evaluation, and Molecular Docking Study

To overcome the multidrug-resistant tuberculosis (MDR-TB) problem, we reported the synthesis of novel sulfonamide-based pyrazole-clubbed pyrazoline derivatives (9a-p) by reaction of 1-(7-chloroquinolin-4-yl)-3-(thiophene/furan-2-yl)-1 H -pyrazole-4-carbaldehyde chalcone derivatives (8a-p) and 4-hydrazinylbenzenesulfonamide (2) in the presence of a catalytic amount of Conc. HCl and ethanol are used as a solvent. Newly synthesized compounds were tested against the Mycobacterium tuberculosis H 37 Rv strain, wherein compounds 9g , 9h , 9i , 9j , 9m , and 9n were found to be the most potent. The structures of the newly synthesized analogues were determined by different spectroscopic techniques like ESI-MS, FT-IR, NMR, and UV methods. Additionally, molecular docking studies of the active site of mycobacterial InhA resulted in well-aggregated elucidations for these compounds with a binding strength in the range of -9.714 to -8.647 . Compound 4-(1'-(7-chloroquinolin-4-yl)-5-(4-fluorophenyl)-3'-(thiophen-2-yl)-3,4-dihydro-1 'H ,2 H -[3,4'-bipyrazol]-2-yl)benzenesulfonamide (9g) shows excellent antitubercular activity against M. tuberculosis H 37 Rv, achieving an MIC of 10.2 μg/mL and 99% inhibition with a docking score of -9.714 and a Glide energy of -64.183 kcal/mol . In silico ADMET predictions indicated the drug-likeness of synthesized novel molecules.