Sulfonamide Moiety as "Molecular Chimera" in the Design of New Drugs

Abstract

Background: The -SO₂NH- group is of great significance in modern pharmaceutical use since, in sulfa-drugs, it is possible to introduce easily chemical modifications, and even small changes may lead to an improved version of an already existing drug.

Objective: This paper aims to describe updated information in the sulfonamide field with a particular focus on new mechanisms of action, especially if discovered by employing computational approaches.

Methods: Research articles that focused on the use of the sulfonamide moiety for the design, synthesis, and in vitro/in vivo tests of various diseases were collected from various search engines like PubMed, Science Direct, Google Scholar, and Scopus, using keywords like sulfonamide moiety, aryl/heteroary lsulfonamides, alkyl sulfonamides, in silico drug design, etc. Conclusion: The more relevant reports highlighting the prominent role of sulfonamide moiety in drug discovery have been critically analyzed. Sulfonamides can be considered as "molecular chimera", which are found to form hydrogen bonds as well as interact with unipolar environments within proteins. Therefore, based on the analysis reported herein, it is strongly foresight that new entities can be developed easily to improve the available machinery helpful in the fight against new and emerging diseases.

Keywords: Sulfonamide moiety; alkyl sulfonamides; aryl/heteroaryl sulfonamides; docking; in silico drug design; molecular chimera; molecular dynamics; pharmacophore modeling.