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

Area of Science:

• Medicinal Chemistry
• Organic Synthesis
• Antimicrobial Agents

Background:

• Multidrug-resistant tuberculosis (MDR-TB) poses a significant global health threat.
• Development of novel therapeutic agents is crucial for effective tuberculosis treatment.

Purpose of the Study:

• To synthesize and characterize novel sulfonamide-based pyrazole-clubbed pyrazoline derivatives.
• To evaluate the in vitro antimycobacterial activity of synthesized compounds against Mycobacterium tuberculosis H37Rv.
• To investigate the binding interactions of active compounds with the mycobacterial InhA enzyme through molecular docking.

Main Methods:

• Synthesis of target compounds (9a-p) via reaction of chalcone derivatives with 4-hydrazinylbenzenesulfonamide.
• Spectroscopic characterization using ESI-MS, FT-IR, NMR, and UV-Vis spectroscopy.
• Antitubercular activity screening and determination of Minimum Inhibitory Concentration (MIC).
• Molecular docking studies against the InhA enzyme active site.
• In silico ADMET predictions for drug-likeness.

Main Results:

• Successful synthesis of novel sulfonamide-based pyrazole-clubbed pyrazoline derivatives (9a-p).
• Compounds 9g, 9h, 9i, 9j, 9m, and 9n exhibited potent activity against M. tuberculosis H37Rv.
• Compound 9g showed excellent activity with an MIC of 10.2 μg/mL, 99% inhibition, and a docking score of -9.714.
• Molecular docking revealed strong binding affinities for active compounds with the InhA enzyme.
• In silico ADMET predictions suggested favorable drug-like properties for the synthesized molecules.

Conclusions:

• The synthesized sulfonamide-based pyrazole derivatives represent a promising class of compounds for developing new anti-tuberculosis agents.
• Compound 9g is identified as a lead candidate with significant antimycobacterial potential.
• Further investigation into the mechanism of action and in vivo efficacy of these compounds is warranted.