Synthesis of beta-hydroxypropanoic acid derivatives as potential anti-inflammatory, analgesic and antimicrobial agents.
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.
Abdel-Rahman
Hamdy M
HM
Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Assiut University, Assiut, Egypt. hamdym@acc.aun.edu.eg
Hussein
Mostafa A
MA
D000700:Analgesics / Q000138:chemical synthesis / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000494:pharmacology* / Q000627:therapeutic use; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000494:pharmacology* / Q000627:therapeutic use; D000935:Antifungal Agents / Q000138:chemical synthesis / Q000494:pharmacology* / Q000627:therapeutic use; D001230:Aspergillus / Q000187:drug effects; D001241:Aspirin / Q000494:pharmacology / Q000627:therapeutic use; D001419:Bacteria / Q000187:drug effects; D002351:Carrageenan; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control; D015725:Fluconazole / Q000494:pharmacology / Q000627:therapeutic use; D006614:Hindlimb / Q000187:drug effects / Q000473:pathology; D007213:Indomethacin / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008826:Microbial Sensitivity Tests / Q000379:methods; D015394:Molecular Structure; D010400:Penicillin G / Q000494:pharmacology / Q000627:therapeutic use; D011422:Propionates / Q000138:chemical synthesis / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D023382:Toxicity Tests, Acute / Q000379:methods; D014456:Ulcer / Q000139:chemically induced / Q000517:prevention & control
D000700:Analgesics; D000900:Anti-Bacterial Agents; D000893:Anti-Inflammatory Agents; D000935:Antifungal Agents; D011422:Propionates; D015725:Fluconazole; D002351:Carrageenan; D010400:Penicillin G; D001241:Aspirin; D007213:Indomethacin