Thiophene-Based Compounds with Potential Anti-Inflammatory Activity

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.

AB0273 HYPERSENSIVITY REACTIONS TO NON STEROID ANTI INFLAMMATORY DRUGS: A BOUT 87 CASES

Background:Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the leading causes of hypersensitivity reactions to drugs. The pathogenesis may be immunological mechanisms (allergic reactions) or non specific immunological reactions often incriminated in cross reactivity independently of chemical structure of these molecules. Understanding of the underlying mechanism is necessary for prevention and choice of safe alternatives [1, 2].Objectives:Analyze all cases of non-steroidal anti-inflammatory drugs cutaneous eruption reported to sfax pharmacovigilance service since January 2015 to December 2020 and evaluate the possibility of cross-reactions between different molecules in this class.Methods:We conducted a retrospective study of all cases reported to sfax pharmacovigilance department. An enquiry of pharmacovigilance was performed in patients who presented side effects to AINS. The imputability study was carried out by the French method of Imputability. Medical history specifies if there is a re-administration to assess tolerance and cross-reactivity.Results:Our study included 87 patients whose average age was 45, 8 years. The sex ratio (F/M) was 1.18. lysine salicylate acetyl is the most incriminated (31%), then mefenamic acid (19.5%), diclofenac (19.5 %), ketoprofen in (9.2%), piroxicam in (6.9 %), ibuprofen in (5.4%), celocoxib in (3.4%), tiaprofenic acid in (1.1%) and naproxen in 1.1% of cases. The most common skin injury was urticaria in 29 cases (33.3%). Fixed drug eruption was observed in 17 cases. Maculopapular rash was observed in 19 cases, anaphylaxis in 5 cases and 4 cases of photosensitivity were observed. In our study we found cross-reactivity between (NSAIDs) in 8 patients.Conclusion:The diagnostic approach is often based on the controlled administration of the drug to assess tolerance and to identify safe alternatives. In cases of intolerance to COX 1 inhibitors, cross-reactions to selective cox 2 inhibitors are very rare [3].References:[1]Inmaculada Dona, Maria Salas, James R Perkins and al. Hypersensitivity Reactions to Non-Steroidal Anti-Inflammatory Drugs. Curr Pharm Des 2016; 22(45):6784-6802.[2]Flavia Angeletti, Franziska Meier, Nadja Zöller, Markus Meissner, Roland Kaufmann, Eva Maria Valesky. Hypersensitivity reactions to non-steroidal anti-inflammatory drugs (NSAIDs) - a retrospective study. J Dtsch Dermatol Ges 2020 Dec; 18(12):1405-1414.[3]N Blanca-López, J A Cornejo-García, M C Plaza-Serón, and al. Hypersensitivity to Nonsteroidal Anti-inflammatory Drugs in Children and Adolescents: Cross-Intolerance Reactions. J Investig Allergol Clin Immunol 2015; 25(4):259-69.Disclosure of Interests:None declared

Recent Achievement in the Synthesis of Thiophenes

: Thiophene derivatives are aromatic five-membered ring compounds made up of one Sulphur as heteroatom. These compounds are present in a large number of natural and unnatural compounds with valuable bioactivities. Many of them have a wide range of applications in medicinal chemistry such as antimicrobial, anticancer, antiparasitic, anti-inflammatory, and antihypertensive activities. Some of them are famous drugs in the market nowadays such as Cefoxitin, Cephalothin, Cephaloridine, Temocillin, tinoridine, tiaprofenic acid, tenoxicam, suproprofen and Raltitrexed. The use of thiophenes derivatives also has been found in other fields. The application of thiophenes in organic materials thank to their electronic properties has been reported. In organic synthesis, thiophenes also have drawn attention of chemists because of their values as intermediates. The employment of thiophene derivatives in agrochemicals, flavors, and dyes has also been found. Due to diverse applications, the synthesis of thiophene derivatives has attracted a lot of attention. Numerous known synthetic methods such as Gewald and Fiesselmann methods have been modified and improved. Furthermore, a large number of novel synthetic approaches to the synthesis of thiophenes have been developed. This review will focus on considerable studies on the synthesis of thiophenes which date back from 2012. In this review, we discussed recent achievement in the synthesis of thiophene derivatives. Some established methods have been modified and improved, while other novel methods have been discovered. Diverse catalysts were employed for these transformations. In some syntheses, reaction mechanisms were also displayed. Many methods for the synthesis of thiophenes have been developed recently. In the near future, more imaginative approaches for the synthesis of thiophenes will be investigated to improve the efficiency and versatility or to use environmentally friendly and economical procedures. Application to natural product synthesis and drug synthesis is probably the next challenge in the field.

Spectroscopic and chromatographic investigation of chiral interactions between tiaprofenic acid and alginate–metal-complexes

Five alginate–metal-complexes were prepared in the form of beads. ESR and ee% were reported in some cases indicating chiral interactions between Tia and alginate–metal-complexes. IR investigation was carried out to give proof for these interactions.