COX-2 inhibitors in inflammation and cancer: Recent developments in medicinal chemistry

Chronic inflammation is being recognised as a pivotal contributor to the onset and progression of cancer and other severe conditions. The cyclooxygenase (COX) is an essential enzyme in inflammation. Although this enzyme is typically overexpressed by inflammation, in many diseases like liver cirrhosis, thyroiditis, multiple sclerosis, neurological disorders, rheumatoid arthritis, Crohn's disease, ulcerative colitis, and cancer, its level increases persistently. This consistent expression contributes to its crucial role in tumour initiation and development. Additionally, COX-2 plays a dual role, generating both pro- and anti-inflammatory mediators, highlighting its multifaceted, dichotomous nature. Because of its dual role and significant implication in several diseases, it is now seen as a vital target in medicinal chemistry, leading to the development of drugs that specifically block its activity. In this work, we focus on the strong correlation between long-term inflammation and cancer. Furthermore, it explains the key molecular processes involved in this link. It also provides an overview of recent progress in clinical trials, along with FDA-approved drugs, showing their role and importance in treating such conditions. Recent developments over the last seven years (2020-2026) have been analysed, with a particular focus on scaffolds bearing five-membered azole-based heterocyclic compounds. It also provides an insightful resource for medicinal chemists working on the rational design and development of new molecules for the management of inflammation and cancer. Furthermore, oncologists and pharmacologists need to understand the evolving therapeutic model for COX-2-targeted drugs.