Thiophene-Based Compounds with Potential Anti-Inflammatory Activity

Abstract

Rheumatoid arthritis, arthrosis and gout, among other chronic inflammatory diseases are public health problems and represent major therapeutic challenges. Non-steroidal anti-inflammatory drugs (NSAIDs) are the most prescribed clinical treatments, despite their severe side effects and their exclusive action in improving symptoms, without effectively promoting the cure. However, recent advances in the fields of pharmacology, medicinal chemistry, and chemoinformatics have provided valuable information and opportunities for development of new anti-inflammatory drug candidates. For drug design and discovery, thiophene derivatives are privileged structures. Thiophene-based compounds, like the commercial drugs Tinoridine and Tiaprofenic acid, are known for their anti-inflammatory properties. The present review provides an update on the role of thiophene-based derivatives in inflammation. Studies on mechanisms of action, interactions with receptors (especially against cyclooxygenase (COX) and lipoxygenase (LOX)), and structure-activity relationships are also presented and discussed. The results demonstrate the importance of thiophene-based compounds as privileged structures for the design and discovery of novel anti-inflammatory agents. The studies reveal important structural characteristics. The presence of carboxylic acids, esters, amines, and amides, as well as methyl and methoxy groups, has been frequently described, and highlights the importance of these groups for anti-inflammatory activity and biological target recognition, especially for inhibition of COX and LOX enzymes.

The Ethnopharmacological Uses, Metabolite Diversity, and Bioactivity of Rhaponticum uniflorum (Leuzea uniflora): A Comprehensive Review

“…The presented data indicate a good degree of knowledge of the metabolites of the roots and herb of R. uniflorum . Of particular interest are the anti-inflammatory components of R. uniflorum , such as sesquiterpenes [ 84 ], ecdysteroids [ 85 ], triterpenes [ 86 ], thiophenes [ 87 ], and flavonoids [ 88 ]. Owing to the confirmed presence of these compounds in the plant, we understand its ethnopharmacological use as an anti-inflammatory agent.…”

Thiophenes—Naturally Occurring Plant Metabolites: Biological Activities and In Silico Evaluation of Their Potential as Cathepsin D Inhibitors

“…In our previous review, 96 natural thiophene derivatives were listed from various plant species belonging to the Asteraceae family till 2015, with a particular focus on their biosynthesis, bioactivities, and physical and spectral data [8]. Recently, several reviews dealing with synthetic thiophene-based derivatives, including their anti-inflammation and anticancer potentials, spectroscopic properties, and synthesis, were published [21][22][23][24]. On the other side, there is no available review on naturally occurring thiophene derivatives from plant sources.…”

Synthesis, X-ray structure, antimicrobial activity, DFT and molecular docking studies of N-(thiophen-2-ylmethyl)thiophene-2-carboxamide

“…Among five-membered heteroaromatic rings, thiophene has been widely used as a building block in drug molecules and plays an important role in various biochemical processes. Thanks to the presence of the thiophene unit and with an additional amide functional group in their structure, thiophene-based amides have been reported to possess a wide variety of biological and pharmacological activities, including antibacterial (Koparır & Parlak, 2018), antifungal (Kheder & Mabkhot, 2012;Refat & Fadda, 2013), anticancer (Archna et al, 2020) anti-inflammatory (da Cruz et al, 2021), antidepressant (Wardakhan et al, 2008), glucagon receptor (GCGR) antagonist (Li et al, 2018), allosteric enhancers for A1 adenosine receptor (Baraldi et al, 2007), in the treatment of osteoporosis (Marchais-Oberwinkler et al, 2013) and anti-HIV (Kheder & Mabkhot, 2012). Furthermore, thiophene-based molecules exhibit various other applications, e.g.…”