Efficient Synthesis and In Vitro Biological Evaluation of 2,5‐Diaryloxazoles as Potential Nitric Oxide Production Inhibitors

Abstract

An efficient first synthesis of 2,5‐diaryloxazoles 1–5 was accomplished from commercially inexpensive precursors and in overall yields of 38–48%. The synthesis proceeds via α‐aminoketones and cyclodehydration (Robinson–Gabriel reaction) as key step. Next, these oxazoles were examined for their inhibitory effect against nitric oxide (NO) production in lipopolysaccharide (LPS)‐induced RAW 264.7 cells and were found to display concentration‐dependent inhibition of NO production without cytotoxicity. Of note, compound 3 (70.7%; IC50 = 2.33 μM) was identified as a potent inhibitor in view of its comparable inhibitory effect with the positive control, N G‐monomethyl‐L‐arginine acetate (L‐NMMA) (79.3%; IC50 = 4.51 μM) followed by compounds 5 (68.3%; IC50 = 2.30 μM) and 2 (53.9%; IC50 = 6.31 μM). As a whole, compound 3 may hold great promise for further development of NO production targeted anti‐inflammatory agent.

Fluorescence Spectroscopic Studies on the Interaction Between 2,5‐Diphenyl Oxazole and Triton X‐100 Micelle

“…In current years, its research has increase considerable attention from both industry and academia in view of its assorted pharmacological properties . Some oxazoles showed inhibitory activity of enzyme as well as against nitric oxide (NO) production in lipopolysaccharide (LPS)‐induced RAW 264.7 cells . The reports available on substituted oxazoles can be used as agrochemicals, fluorescent dyes, corrosion inhibitors and find applications in photography and polymer industries .…”

“…Mostly, 2,5‐substituted aryl or alkyl oxazoles are advantaged scaffolds found in numerous natural products and pharmaceutical agents . They have been examined as antidiabetic, anticancer, and antibacterial agents . Yet, oxazole‐type alkaloids are rare natural products the oxazole structure is found as an essential moiety of certain pharmaceuticals and drug candidate compounds, containing aleglitazar and oxaprozin.…”