Synthesis, biological evaluation and SAR study of novel pyrazole analogues as inhibitors of Mycobacterium tuberculosis

• Published in: Bioorganic & medicinal chemistry Vol. 16; no. 18; pp. 8587 - 8591
• Main Authors: Castagnolo, Daniele, De Logu, Alessandro, Radi, Marco, Bechi, Beatrice, Manetti, Fabrizio, Magnani, Matteo, Supino, Sibilla, Meleddu, Rita, Chisu, Lorenza, Botta, Maurizio
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 15-09-2008; Elsevier
• Subjects: 5-Hydroxy-pyrazole; Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antitubercular Agents - chemical synthesis; Antitubercular Agents - pharmacology; Biological and medical sciences; Medical sciences; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Mycobacterium tuberculosis - drug effects; Pharmacology. Drug treatments; Pyrazoles - chemical synthesis; Pyrazoles - pharmacology; Pyrazolone; SAR study; Structure-Activity Relationship; Tuberculosis; Tuberculosis; Pyrazolone; SAR study; 5-Hydroxy-pyrazole; Combinatorial chemistry; In vitro; Mycobacterium tuberculosis; Structure activity relation; Mycobacteriales; Mycobacteriaceae; Pyrazole derivatives; Bacteria; Actinomycetes; Antituberculous agent; Antibacterial agent; Chemical synthesis; Halogen Organic compounds
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2008.08.016

As a continuation of our previous work that turned toward the identification of antimycobacterial compounds with innovative structures, two series of pyrazole derivatives were synthesized by parallel solution-phase synthesis and were assayed as inhibitors of
Mycobacterium tuberculosis (MTB), which is the causative agent of tuberculosis. One of these compounds showed high activity against MTB (MIC
=
4
μg/mL). The newly synthesized pyrazoles were also computationally investigated to analyze their fit properties to the pharmacophoric model for antitubercular compounds previously built by us and to refine structure–activity relationship analysis.