Sulfonamides as tyrosine kinase modulators – A promising class of anticancer agents

Abstract

Tyrosine kinases are significant mediators of the signaling cascade that play vital role in various biological processes. The involvement of tyrosine kinases in regulating and functioning various metabolic pathways in the body has encouraged scientists to study their role in cancer onset and progression extensively. The human genome consists of over 90 tyrosine kinases, making it a wider research domain. To date, drugs incorporating a wide variety of heterocyclic scaffolds have been developed against many tyrosine kinases. However, factors such as drug resistance, undesirable side effects, and toxicity shown by current anticancer agents are significant challenges. These shortcomings compelled medicinal chemists to ponder the development of variable scaffolds with proficient anticancer activity and minimum toxicity. After the discovery of prontosil (the first sulfonamide antibiotic), molecules with sulfonamide moiety were synthesized and tested for bacterial infections, diabetes, inflammation, glaucoma, etc. and soon sulfonamides with oncotherapeutic effects surfaced. ACK1/TNK, BTK, LMTK3, and EGFR, etc., are some of the enzymes belonging to receptor tyrosine kinase family which are customarily mutated or overexpressed in different types of cancer. These enzymes are now widely explored and modulators of these enzymes having the sulfonamide moiety are steadily being launched. In this review we sight to summarize the chemical and biological aspects of these sulfonamide containing compounds as tyrosine kinase modulators and their role in preventing and terminating the progression of cancer.