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 by reaction of 1-(7-chloroquinolin-4-yl)-3-(thiophene/furan-2-yl)-1-pyrazole-4-carbaldehyde chalcone derivatives and 4-hydrazinylbenzenesulfonamide in the presence of a catalytic amount of Conc. HCl and ethanol are used as a solvent. Newly synthesized compounds were tested against the HRv strain, wherein compounds , , , , , and 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 to . Compound 4-(1'-(7-chloroquinolin-4-yl)-5-(4-fluorophenyl)-3'-(thiophen-2-yl)-3,4-dihydro-1,2-[3,4'-bipyrazol]-2-yl)benzenesulfonamide shows excellent antitubercular activity against M. tuberculosis HRv, achieving an MIC of and inhibition with a docking score of and a Glide energy of . In silico ADMET predictions indicated the drug-likeness of synthesized novel molecules.