Thiazoles and Thiazolidinones as COX/LOX Inhibitors

Abstract

Inflammation is a natural process that is connected to various conditions and disorders such as arthritis, psoriasis, cancer, infections, asthma, etc. Based on the fact that cyclooxygenase isoenzymes (COX-1, COX-2) are responsible for the production of prostaglandins that play an important role in inflammation, traditional treatment approaches include administration of non-steroidal anti-inflammatory drugs (NSAIDs), which act as selective or non-selective COX inhibitors. Almost all of them present a number of unwanted, often serious, side effects as a consequence of interference with the arachidonic acid cascade. In search for new drugs to avoid side effects, while maintaining high potency over inflammation, scientists turned their interest to the synthesis of dual COX/LOX inhibitors, which could provide numerous therapeutic advantages in terms of anti-inflammatory activity, improved gastric protection and safer cardiovascular profile compared to conventional NSAIDs. Τhiazole and thiazolidinone moieties can be found in numerous biologically active compounds of natural origin, as well as synthetic molecules that possess a wide range of pharmacological activities. This review focuses on the biological activity of several thiazole and thiazolidinone derivatives as COX-1/COX-2 and LOX inhibitors.

Evaluation of Anticonvulsant Activity of Dual COX-2/5-LOX Inhibitor Darbufelon and Its Novel Analogues

“…In the aforementioned context, the darbufelone-NSAID, a dual inhibitor targeting COX-2 and 5-lipoxygenase (5-LOX), presents interest for study as a possible potential anticonvulsant. Darbufelone belongs to 4-thiazolidinone derivatives, and among this class of heterocycles, the thiazole-4-thiazolidinone hybrid molecules are known as an important source of drug-like molecules with various kinds of biological activities as well as polypharmacological agents [24][25][26][27][28][29]. The thiazole-4-thiazolidinone-bearing hybrids with promising anticonvulsant properties were identified and reported [26,30].…”

Pharmacokinetics and Metabolism of Liposome-Encapsulated 2,4,6-Trihydroxygeranylacetophenone in Rats Using High-Resolution Orbitrap Liquid Chromatography Mass Spectrometry

“…Our research group has demonstrated its anti-inflammatory properties, including the airway inflammation, with a potency comparable to clinically used drugs (Zileuton and Ketotifen), in several in vitro and in vivo studies [2][3][4][5][6][7][8][9]. The dual COX-2/5-LOX inhibition activity of tHGA makes it a promising anti-inflammatory and anti-allergic drug with fewer adverse effects [10].…”

Oxidative Stress and Lipid Mediators Modulate Immune Cell Functions in Autoimmune Diseases

“…It is well known that oxidative stress promotes modification of lipid metabolism [ 34 , 73 , 74 ]. Oxidative conditions have been shown to promote the activation of enzymes such as phospholipase, cyclooxygenases (COX), lipoxygenases (LOX), and cytochrome p450 (CYP450) [ 75 ], which are involved in the metabolism of lipids and their derivatives, resulting in the formation of eicosanoids, which are, in turn, involved in modulation of the redox balance and inflammation by activating specific receptors. Phospholipids are also metabolized by N-acyltransferase (NAT), phospholipase C (PLC), diacylglycerol lipase (DAGL), and N-acylphosphatidylethanolamine phospholipase D (NAPE-PLD) into endocannabinoids ( Figure 5 ) [ 76 , 77 ].…”

“…The main substrate of cyclooxygenases is arachidonic acid (AA), which is released from phospholipids by phospholipase A 2 [ 75 ]. Due to COX activity, AA is metabolized into two-series eicosanoids, initially resulting in the formation of prostaglandin G 2 (PGG 2 ), which is subsequently reduced to PGH 2 , after which it is rapidly converted to other prostaglandins (e.g., PGE 2 , PGF 2 , PGD 2 , PGI 2 ) and thromboxanes (e.g., thromboxane A 2 ) via specific prostaglandin and thromboxane synthases [ 102 ].…”