Synthesis and biological evaluation of pyrazolylthiazole carboxylic acids as potent anti-inflammatory–antimicrobial agents

• Published in: Bioorganic & medicinal chemistry letters 2015-03, Vol.25 (6), p.1177-1181
• Main Authors: Khloya, Poonam, Kumar, Satish, Kaushik, Pawan, Surain, Parveen, Kaushik, Dhirender, Sharma, Pawan K.
• Format: Article
• Language: English
• Subjects: Animals; Anti-Infective Agents - chemical synthesis; Anti-Infective Agents - pharmacology; Anti-Infective Agents - therapeutic use; Anti-inflammatory activity; Anti-Inflammatory Agents - chemical synthesis; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; Antimicrobial activity; Carboxylic Acids - chemistry; Carboxylic Acids - pharmacology; Carboxylic Acids - therapeutic use; Edema - chemically induced; Edema - drug therapy; Fungi - drug effects; Gram-Positive Bacteria - drug effects; Indomethacin - pharmacology; Indomethacin - therapeutic use; Microbial Sensitivity Tests; Pyrazole; Pyrazoles - chemistry; Rats; Thiazole; Thiazoles - chemistry
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2015.02.004

[Display omitted] Current Letter presents design, synthesis and biological evaluation of a novel series of pyrazolylthiazole carboxylates 1a–1p and corresponding acid derivatives 2a–2p. All 32 novel compounds were tested for their in vivo anti-inflammatory activity by carrageenan-induced rat paw edema method as well as for in vitro antimicrobial activity. All the tested compounds exhibited excellent AI activity profile. Three compounds 1p (R=Cl, R1=Cl), 2c (R=H, R1=F) and 2n (R=Cl, R1=OCH3) were identified as potent anti-inflammatory agents exhibiting edema inhibition of 93.06–89.59% which is comparable to the reference drug indomethacin (91.32%) after 3h of carrageenan injection while most of the other compounds displayed inhibition ⩾80%. In addition, pyrazolylthiazole carboxylic acids (2a–2p) also showed good antimicrobial profile. Compound 2h (R=OCH3, R1=Cl) showed excellent antimicrobial activity (MIC 6.25μg/mL) against both Gram positive bacteria comparable with the reference drug ciprofloxacin (MIC 6.25μg/mL).