New ibuprofen derivatives with thiazolidin-4-one scaffold with improved pharmaco-toxicological profile

Abstract

Background Aryl-propionic acid derivatives with ibuprofen as representative drug are very important for therapy, being recommended especially for anti-inflammatory and analgesic effects. On other hand 1,3-thiazolidine-4-one scaffold is an important heterocycle, which is associated with different biological effects such as anti-inflammatory and analgesic, antioxidant, antiviral, antiproliferative, antimicrobial etc. The present study aimed to evaluated the toxicity degree and the anti-inflammatory and analgesic effects of new 1,3-thiazolidine-4-one derivatives of ibuprofen. Methods For evaluation the toxicity degree, cell viability assay using MTT method and acute toxicity assay on rats were applied. The carrageenan-induced paw-edema in rat was used for evaluation of the anti-inflammatory effect while for analgesic effect the tail-flick test, as thermal nociception in rats and the writhing assay, as visceral pain in mice, were used. Results The toxicological screening, in terms of cytotoxicity and toxicity degree on mice, revealed that the ibuprofen derivatives (4a-n) are non-cytotoxic at 2 µg/ml. In addition, ibuprofen derivatives reduced carrageenan-induced paw edema in rats, for most of them the maximum effect was recorded at 4 h after administration which means they have medium action latency, similar to that of ibuprofen. Moreover, for compound 4d the effect was higher than that of ibuprofen, even after 24 h of administration. The analgesic effect evaluation highlighted that 4 h showed increased pain inhibition in reference to ibuprofen in thermal (tail-flick assay) and visceral (writhing assay) nociception models. Conclusions The study revealed for ibuprofen derivatives, noted as 4 m, 4 k, 4e, 4d, a good anti-inflammatory and analgesic effect and also a safer profile compared with ibuprofen. These findings could suggest the promising potential use of them in the treatment of inflammatory pain conditions.

Exploring ibuprofen derivatives as α‐glucosidase and lipoxygenase inhibitors: Cytotoxicity and in silico studies

“…Various derivatives of ibuprofen moiety into a variety of heterocyclic analogs are reported. For example, 1,3,4-oxadiazoles, [42][43][44] 1,3, 4-thiadiazoles, [45,46] 1,2,4-triazine, [47] 1,2,4-triazole, [48] 1,3-thiazolidine-4one, [49] benzimidazole, [50] imidazopyrazine, [51] heteroatomic amines and amides, [52,53] furoxan, [54,55] polyethylene glycol (PEG), [56] poly(oxyethylene), [57] 1,1-di-(3-carboxyphenyl)ethane derivatives, [58] biodegradable polyesters, [59] and Schiff and Mannich bases. [60] The activity of ibuprofen itself was evaluated to control Staphylococcus aureus biofilms, [61] and its derivatives (hybridized with H 2 S-or NO-donating moieties) were investigated for anti-inflammatory and ulcerogenic potential.…”