Thiophene-Based Compounds with Potential Anti-Inflammatory Activity.

Ryldene Marques Duarte Da Cruz,Francisco Jaime Bezerra Mendonça-Junior,Reinaldo Nóbrega De Almeida,Rodrigo Santos Aquino De Araújo,Natália Barbosa De Mélo,Ricardo Olímpio De Moura,Luciana Scotti

doi:10.3390/ph14070692

Ryldene Marques Duarte Da Cruz, Francisco Jaime Bezerra Mendonça-Junior + Show 5 more

Open Access

https://doi.org/10.3390/ph14070692

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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.

Highlights

Inflammation is a tightly and carefully regulated, protective process, both complex and multifactorial, and mounted by the innate immune system in response to harmful stimuli such as ischemia, tissue damage, autoimmune injuries, dead cells, pathogens, toxins, and chemicals
These results indicate that thiophene pyrazole hybrids are promising anti-inflammatory drug candidates with moderate and selective Cyclooxygenase enzymes (COX)-2 inhibition
This review demonstrates the importance of thiophene-based compounds as privileged structures in drug design and in discovery of novel anti-inflammatory agents

Summary

Introduction

Inflammation is a tightly and carefully regulated, protective process, both complex and multifactorial, and mounted by the innate immune system in response to harmful stimuli such as ischemia, tissue damage, autoimmune injuries, dead cells, pathogens, toxins, and chemicals. The mechanisms involved in this process are characterized by a complex series of events that involve changes in vascular permeability, exudation of fluids containing plasma proteins, and migration cells within the immune system, such as leukocytes, lymphocytes, and macrophages into the inflammatory area [1,2,3,4,5] These mechanisms are mediated through a great variety of soluble micromolecules, which include several secreted polypeptides known as cytokines. Tinoridine, Tiaprofenic acid, Tenidap, and Zileuton (Figure 1) are the best-known examples ofcommercially commerciallyavailable availabledrugs drugswith withanti-inflammatory anti-inflammatoryproperties propertiesthat thatcontain contain examples of thiophenering ringas aspharmacophoric pharmacophoric group. Pharmaceuticals 2021, 14, 692 most promising compounds and anti-inflammatory substitution patterns, and to help direct the synthesis of potentially more active new derivatives. The keywords that were combined and used in the search were: inflammation, thiophene, pyrexia and in

The Role of Thiophene Derivatives in Inflammation

Findings

Conclusions