Synthesis of β-Hydroxypropanoic Acid Derivatives as Potential Anti-inflammatory, Analgesic and Antimicrobial Agents

✍ Scribed by Hamdy M. Abdel-Rahman; Mostafa A. Hussein

• Publisher: John Wiley and Sons
• Year: 2006
• Tongue: English
• Weight: 614 KB
• Volume: 339
• Category: Article
• ISSN: 0365-6233
• DOI: 10.1002/ardp.200600016

✦ Synopsis

Abstract

A series of new 3‐(substituted) 3‐hydroxy‐propanoic acid ethyl esters 1a–c, hydrazides 2a–c, thiosemicarbazides 3a–f, and semicarbazides 3g, 3h has been synthesized. Cyclization of compounds 3a–d in basic medium yielded 1,2,4‐triazole‐5‐thiones 4a–d. On the other hand, reaction of hydrazides 2a–c with CS~2~ in basic medium afforded 1,3,4‐oxadiazole‐5‐thiones 5a–c. All the synthesized compounds were characterized by their physical and spectral analyses data. The newly synthesized compounds were evaluated for their anti‐inflammatory, analgesic, and antimicrobial activities. Compounds 1c, 3g, 4a, 4b, 4c, and 5c exhibited comparable anti‐inflammatory activity to that of indomethacin and compounds 1c, 4c, and 5c were more analgesics than acetyl salicylic acid. Compounds 4b, 4c, and 5c showed superior GI safety profile (33.3%, 33.3% and 50.0% ulceration) than that of indomethacin (100% ulceration) at 100 mg/kg oral dose. Compounds 4b, 4c, and 5c were also non‐toxic with a median lethal dose (LD~50~) up to 200 mg/kg. The antibacterial and antifungal screenings identified compounds 3c, 4b, 4d, 5a, and 5b as the most effective against a variety of tested microorganisms.