dual cox-2/tnf-α inhibitors as promising anti-inflammatory and cancer chemopreventive agents: a review

Cyclooxygenases (cox) play a pivotal role in inflammation and are responsible for the production of prostaglandins (pgs). two types of coxs have been identified as key biological targets for drug design: constitutive cox-1 and inducible cox-2. nonsteroidal anti-inflammatory drugs (nsaids) target cox-1, while selective cox-2 inhibitors are designed for cox-2. these cox isoforms are involved in multiple physiological and pathological pathways throughout the body. overproduction of tumor necrosis factor-alpha (tnf-α) plays a role in cox-2's inflammatory activity. tumor necrosis factor-alpha can contribute to cardiac fibrosis, heart failure, and various cancers by upregulating the cox-2/pge2 axis. therefore, suppressing cox activity has emerged as a potentially effective treatment for chronic inflammatory disorders and cancer. this review explores the mechanisms of tnf-α-induced cox-2/pge2 expression, a significant pathophysiological feature of cancer development. furthermore, we summarize chemical compounds with dual cox-2/tnf-α inhibitory actions, providing an overview of their structure-activity relationship. these insights may contribute to the development of new generations of dual-acting cox-2/tnf-α inhibitors with enhanced efficacy.