Synthesis and evaluation of anti-inflammatory, analgesic, ulcerogenic and lipid peroxidation properties of ibuprofen derivatives

Abstract

In order to reduce the ulcerogenic effect of ibuprofen, its carboxylic group has been converted into 5-membered heterocyclic rings. Various 1,3,4-oxadiazoles (3-8, 16-21), 1,2,4-triazoles (22-27), 1,3,4-thiadiazoles (28-30), and 1,2,4-triazine (9) derivatives of ibuprofen were prepared by cyclization of 2-(4-i-butylphenyl) propionic acid hydrazide (2) and N1-[2-(4-i-butylphenyl)-propionyl]-N4-alkyl/aryl-thiosemicarbazides (10-15) under various reaction conditions. The cyclized derivatives were screened for their anti-inflammatory activity by the carrageenan induced rat paw edema method and showed 50 to 86% inhibition, whereas the standard drug ibuprofen showed 92% inhibition at the same oral dose. Five compounds, 7, 16, 18, 22 and 30 that showed more than 80% anti-inflammatory activity were selected to study their analgesic, ulcerogenic and lipid peroxidation activities. All the tested compounds showed a significant reduction in ulcerogenic activity compared to ibuprofen through the severity index 0.5 to 0.8, vs. ibuprofen 1.8. The compounds, that showed less ulcerogenic effect also produced less malondialdehyde content in gastric mucosa, which is one of the end products of lipid peroxidation. The results of biological studies showed that oxadiazole derivative 16 as the lead molecule with maximum anti-inflammatory, analgesic and minimum ulcerogenic and lipid peroxidation activities.

DFT Investigation of Chelation of Divalent Cations by Some 4-Benzylidenamino-4,5-Dihydro-1H-1,2,4-Triazol-5-One Derivatives

“…The sign of the values of Gibb energies for the reaction of complexation (1) shows that the complexation is possible in gas and in acetonitrile. In DMF, the complexation with the ligand c is impossible.…”

“…Among the increasing number of heterocyclic nitrogen containing compounds, which are pursued in both industry and academia, 1,2,4 triazole derivatives are also interesting targets for drugs design. In general, 1,2,4 triazole derivatives are biologically versatile compounds displaying a variety of biological effects which include anti-imflammatory [1], antimycobacterial [2][3], antifugal [4], antibacterial [5][6] and antiviral activities [3]. The 4-benzylidenamino-4,5-dihydro-1H-1,2,4-triazol-5-one derivatives obtained through the reaction [7] of 3-alkyl(aryl)-4-amino-4,5-dihydro-1H-1,2,4-triazol-5-ones with 3,4 dihydroxy benzaldehyde, possess various biological properties such as anticonvulsant [7], antifungal [8][9], antituberculosis [10] and antiproliferative [11] activities.…”

Utilization of Cyanoacetohydrazide and Oxadiazolyl Acetonitrile in the Synthesis of Some New Cytotoxic Heterocyclic Compounds

“…Also N-(5-(cyano(4-methyl-3-phenylthiazol-2(3H)-ylidene)methyl)-1,3,4-oxadiazol-2-yl)benzamide which contains the 1,3,4-oxadiazole ring and the nitrile group showed antitumor activity [46]. 1,3,4-Oxadiazole derivatives were synthesized via the reaction of hydrazide derivatives using different reagents such as CS 2 [47], POCl 3 /aromatic carboxylic acid [48], thionyl chloride [49][50][51], triphenylphosphine oxide, [52] silica-supported dichlorophosphate [53] and ZrCl 4 [54]. The syntheses of 1,3,4-oxadiazoles via the Huisgen reaction [55,56] is a less popular methodology than the methods mentioned above.…”

Biological study on novel coumarinyl 1,3,4-oxadiazoles

“…Acetohydrazides were reacted with CS 2 in alkaline medium followed by acidic treatment. 11 1,3,4-Oxadiazoles were also prepared by a reaction of different acylhydrazydes, aromatic acids, and phosphoryl chloride by Amir and Kumar 12 as well as by Khan and Akhtar. 13 Khan and Akhtar…”