Synthesis of New N‐Substituted 5‐Arylidene‐2,4‐thiazolidinediones as Anti‐Inflammatory and Antimicrobial Agents

Abstract

A novel series of 5-arylidene-2,4-thiazolidinediones (TZDs) 2a-p was synthesized from the condensation of 3-((2-phenylthiazol-4-yl)methyl)thiazolidine-2,4-dione with different benzaldehyde derivatives. All the structures were confirmed by their spectral (IR, ¹H NMR, ¹³C NMR and mass) and elemental analytical data. The new molecules were evaluated in vivo as anti-inflammatory agents in an acute experimental inflammation, evaluating the acute phase bone marrow response and phagocyte activity. All compounds, excepting one, reduced the absolute leukocytes count due to the lower neutrophil percentage. Phagocytary index was decreased by the same molecules, while only half of them reduced the phagocytary activity. The effect was superior to meloxicam, the reference anti-inflammatory drug, for the majority of the TZD derivatives. The new molecules were also investigated for their antimicrobial properties on Gram-positive and Gram-negative bacteria and one fungal strain. Two compounds (2e and 2n) manifested growth inhibition capacity on all the tested strains.

5-Ene-4-thiazolidinones – An efficient tool in medicinal chemistry

“…One of the earliest directions of the 5-ene-4-thiazolidinones biological assays lies in the field of antibacterial and antifungal activities search. Apparently, the structural similarity of 4azolidinones with penicillin antibiotics was the stimulus to the study of such type of activity [1e3, 6,167,168]. Though, recently it was discovered that manifestation of antibacterial effect is not always related to the penicillins' mode of action.…”

“…5-Arylidine-2,4-thiazolidinedione derivatives without substituent in the N3 position [371] as well as N3-substituted analogs 147 [372] (Scheme 76) possessed anti-inflammatory activity and related type of activities, such as analgesic activity and in vitro antioxidant activity or even antimicrobial [167]. The structural affinity to PPARg agonists (in silico correlation studies and PPAR-competition binding assay) indicates the possibility of PPAR mediated mode of antiinflanmatory action [372].…”

Design, Synthesis, and Biological Evaluation of Thiazolidine‐2,4‐dione Conjugates as PPAR‐γ Agonists

“…2,4‐Thiazolidinediones (TZDs) are an important class of compounds that enhance insulin action (insulin sensitizers) and promote glucose utilization in peripheral tissue . The chemistry of TZDs has attracted attention as they have been found to reveal several biological activities , such as antihyperglycemic , anti‐inflammatory , antimalarial , antioxidant , antitumor , cytotoxic , antimicrobial , and antiproliferative . Unlike sulfonylurea and biguanides which lead to severe hypoglycemia, TZDs are not associated with such hypoglycemic incidents.…”

Synthesis and bioevaluation of new 5-benzylidenethiazolidine-2,4-diones bearing benzenesulfonamide moiety

“…Thiazolidine-2,4-dione is an important scaffold incorporated in many classes of chemical compounds with interesting biological properties, including antibacterial, antifungal (Aneja et al, 2011;Mentese et al, 2009;Bozdag-Dündar et al, 2007;Desai et al, 2014), antidiabetic (Jain et al, 2013), cytotoxic (Romagnoli et al, 2013;Barros et al, 2012), and anti-inflammatory (Nastasȃ et al, 2013) activities, to name a few. Several drugs bearing thiazolidine-2,4-dione moiety have been approved for clinical applications, for example pioglitazone and rosiglitazone (Baba, 2001;Cheng-Lai and Levine, 2000), which were approved for the treatment of type II diabetes mellitus.…”