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

Affiliation

Vasincu IM(1), Apotrosoaei M(1), Constantin S(1), Butnaru M(2), Vereștiuc L(2), Lupușoru CE(3)(4), Buron F(4), Routier S(5), Lupașcu D(1), Taușer RG(1), Profire L(6).
Author information:
(1)Pharmaceutical Chemistry Department, Faculty of Pharmacy, University of Medicine and Pharmacy "Grigore T. Popa" of Iasi, Iași, Romania.
(2)Biomedical Sciences Department, Faculty of Medical Bioengineering, University of Medicine and Pharmacy "Grigore T. Popa" of Iasi, Iași, Romania.
(3)Pharmacology Department, Faculty of Medicine, University of Medicine and Pharmacy "Grigore T. Popa" of Iasi, Iași, Romania.
(4)Institute of Organic and Analytical Chemistry, Université d'Orléans - Pôle de chimie, Orléans, France.
(5)Institute of Organic and Analytical Chemistry, Université d'Orléans - Pôle de chimie, Orléans, France. [Email]
(6)Pharmaceutical Chemistry Department, Faculty of Pharmacy, University of Medicine and Pharmacy "Grigore T. Popa" of Iasi, Iași, Romania. [Email]

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.