Benzo[a]phenoxazines as potential anti-inflammatory drugs

Inflammation is a growing area of research and a target for intervention that is involved in the pathogenesis of several chronic diseases, such as rheumatoid arthritis, cardiovascular diseases and cancer. The chemical diversity of natural molecules and their derivatives has provided successful drugs for a wide range of diseases, including enzyme inhibitors and gene regulators, making natural products an excellent source of anti-inflammatory drugs. Among the biochemical mediators involved in inflammation, cyclooxygenases (COX) and lipoxygenases (LOX) stand out. COX-2, an inducible isoform of cyclooxygenase, is particularly important, as its expression associated to inflammatory processes and carcinogenesis. LOX, another key enzyme in the metabolism of arachidonic acid, contributes to the formation of leukotrienes, which are also part of the inflammatory response. Selective inhibition of these enzymes has been an effective strategy for developing anti-inflammatory agents with fewer side effects.

Benzo[a]phenoxazines, N-,O-heterocyclic compounds, have attracted attention due to their therapeutic potential, especially as anti-inflammatory and anti-cancer agents, besides promising pharmacological properties. They are known for their ability to inhibit the enzymatic activity of COX-2, which makes them favorable candidates for the treatment of inflammatory conditions.

This study investigates the anti-inflammatory properties of several benzo[a]phenoxazines, specifically assessing their potential as new inhibitors of COX-2 and LOX enzymes. Kinetic assay results revealed that these molecules significantly inhibited cyclooxygenase-2 (COX-2), highlighting their promise as potent anti-inflammatory agents.