Indole-based COX-2 inhibitors: A decade of advances in inflammation, cancer, and Alzheimer's therapy

Abstract

Cyclooxygenase-2 (COX-2), a key enzyme in the cyclooxygenase family, is pivotal in producing pro-inflammatory prostaglandins, driving chronic inflammation and related disorders. Targeting COX-2 with selective inhibitors can mitigate these conditions while avoiding the gastrointestinal and hepatotoxic/nephrotoxic side effects of traditional NSAIDs. However, the selectivity towards COX-2 inhibition has been associated with cardiovascular risks, necessitating the discovery of novel molecular scaffolds avoiding CVS side effects. This review focuses on advancements in Indole-based COX-2 inhibitors from 2013 to 2024, emphasizing their potential in treating inflammation, cancer, and Alzheimer's disease. The Indole scaffold, known for its versatility, allows for comprehensive structure-activity relationship (SAR) analysis, facilitating the development of molecules with enhanced selectivity and potency. Molecules having different substituents attached to the Indole scaffold supported by molecular modeling data, is explored in detail. This review provides an concise overview of the pharmacophore profiles of Indole-based chemotherapeutics, contributing to the development of advanced strategies for selective COX-2 inhibition and addressing the challenges and opportunities in the field.

Keywords: Alzheimer’s; Cancer; Cyclooxygenase-2 (COX-2); Indole; Inflammation.