New ibuprofen derivatives with thiazolidine-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.

Synthesis, Characterization of New Isatin-Ibuprofen Derivatives with Expected Biological Activity

“…Group B: Consists of six rats treated with Ibuprofen as a reference drug in a dose of 50 mg/kg dissolved in DMSO. Groups C-F: Six rats for every four groups (C-F) injected with the tested compounds (5)(6)(7)(8), dissolved in DMSO. In doses that are illustrated in Table 1.…”

“…5 The largest and most important group in NSAIDs is aryl propionic acid derivatives, 6 like ibuprofen, naproxen, ketoprofen, and flurbiprofen; among the most widely used pain killers drugs. 7 The first member of the aryl propionic acid family is ibuprofen, chemically named; 2[4-(2-methyl propyl) phenyl] propionic acid. Ibuprofen is the most frequently used and prescribed NSAID, as an anti-inflammatory, an analgesic, and an antipyretic agent.…”

The Bioactivity of Thiazolidin-4-Ones: A Short Review of the Most Recent Studies

“…Vasincu et al carried out evaluation of ibuprofen derivatives with thiazolidine-4-one scaffold (61a-61n) for their anti-inflammatory and analgesic activities (Figure 25) [62]. The carrageenan-induced paw edema assay was used to assess the anti-inflammatory effect.…”

Discovery of 5-Methylthiazole-Thiazolidinone Conjugates as Potential Anti-Inflammatory Agents: Molecular Target Identification and In Silico Studies

“…On the other hand, thiazolidinone core possesses many different pharmacological activities such as antimicrobial [ 39 , 40 , 41 , 42 ], anti-inflammatory [ 43 , 44 , 45 , 46 ], anti-diabetic [ 47 , 48 , 49 ], anticancer [ 41 , 42 , 50 ], anti-HIV [ 51 , 52 ], antioxidant [ 53 ] and carbonic anhydrase inhibitory potency [ 54 , 55 ]. Pioglitazone and rosiglitazone ( Figure 3 ), used to treat type II diabetes, are also very important thiazolidinone-containing agents approved for human use.…”