COX-2 and 5-LOX are major enzymes implicated in inflammatory processes and have a crucial role in the pathogenesis of inflammatory disorders and malignancies. Designing antagonists that may concurrently interact with several receptors is a viable technique; thus, blocking these two targets with a single chemical compound might provide an efficient therapeutic approach. In-silico approaches have been employed to find polypharmacological inhibitors, especially for drug repurposing and multitarget drug design. Here, virtual screening of designed oxygen-containing heterocyclic series from prior literature was used to locate a feasible dual inhibitor against COX-2 and 5-LOX. Among these, 5-phenyl-2-(pyridin-3-yl)oxazol-4-yl cyclohexyl(methyl)sulfamate (N14) and 5-phenyl-2-(pyridin-4-yl)oxazol-4-yl benzenesulfonate (N16) was found to more promising with good interaction energy against COX-2 (-9.5 and -9.4 kcal/mol) and 5-LOX (-8.6 and -7.6 kcal/mol). Additionally, it also fulfilled the ADME/T parameters revealed to be drug-like, as anticipated by Lipinski's rule of five and Veber's rule. Furthermore, the molecular dynamics, free binding energy and post-processing analysis indicate N14 and N16 appears as a promising candidates with a novel molecular scaffold that could be examined further as a polypharmacological anticancer therapeutic candidate to explore further for the development.
Keywords: 5-LOX; ADME/T; COX-2; In silico; MD simulation; free-energy; molecular docking.