Structure-Based Docking to Identify Anti-Inflammatory Phytochemicals Binding to Cox-2 and 5-Lox

Abstract

The process of inflammation is a complicated physiological reaction to noxious stimuli and is the work of cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX), and is thought to be the cause of chronic inflammatory diseases, including arthritis, asthma, and inflammatory bowel disease. Phytochemicals such as flavonoids, terpenoids, alkaloids have been proposed to be a promising multi-target anti-inflammatory agent, which is safer than traditional NSAIDs because it is associated with gastrointestinal, renal, and cardiovascular side effects. The preclinical animal studies prove that such compounds are effective in reducing paw edema, leukocyte infiltration, and pro-inflammatory cytokines. The complementary structure-based molecular docking experiments identify that there is great hydrogen bonding, hydrophobic and high binding affinities with the important catalytic residues of COX-2 and 5-LOX, which support their dual-inhibitory capacity. Also, phytochemicals of various classes could be used with the help of combinatorics to obtain additive or synergistic effects, to increase efficacy with minimal doses and toxicity. The lack of bioavailability, species-specific differences, and long-term safety data are some challenges that require optimization of formulations and translation studies. The combination of in silico docking with in vivo preclinical models is, in general, a powerful platform of prioritization of phytochemical candidates and their progression to safe and effective multi-targeted anti-inflammatory drugs.