Amino-alcohol Bio-conjugate of Naproxen Exhibits Anti-inflammatory Activity through NF-κB Signaling Pathway

Naproxen sodium (Ns) is a well-known synthetic compound used vastly as a nonsteroidal anti-inflammatory drug (NSAID). Previously, we demonstrated that the hydrogels, made of Ns bio-conjugate (NBC), either with amino alcohol (NBC-1 and 2) or amino acid (NBC-3 and 4), displayed anti-inflammatory properties better than Ns, but the effectiveness was not well explored. Here, we investigated that NBC-2, conjugated with {gamma}-amino alcohol, significantly reduces the expression of pro-inflammatory proteins; such as inducible nitric oxide synthase (iNOS) and cyclooxygenase isoform-2 (COX-2), and the production of pro-inflammatory mediator nitric oxide (NO) in lipopolysaccharide and interferon-{gamma} (LPS/IFN-{gamma}) treated mouse macrophage RAW 264.7 cells, compared with bio-conjugation of {beta}-amino alcohol (NBC-1) or {beta}-amino acid (NBC-3) or -amino acid NBC (NBC-4). NBC-2 decreases the nuclear localization of transcription factors NF-{kappa}B by stabilizing its cytoplasmic functional inhibitor I{kappa}B. Moreover, NBC-2 also displays selective inhibitory effect towards COX-1 enzyme activity as determined by enzymatic assay and in silico molecular docking analysis. Thus, we suggest that NBC-2 may be used as a self-delivery anti-inflammatory drug as compared with other NBCs. TOC Graphic O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=143 SRC="FIGDIR/small/901223v1_ufig1.gif" ALT="Figure 1"> View larger version (26K): org.highwire.dtl.DTLVardef@1ab255borg.highwire.dtl.DTLVardef@121aa6eorg.highwire.dtl.DTLVardef@13c4b86org.highwire.dtl.DTLVardef@1827207_HPS_FORMAT_FIGEXP M_FIG C_FIG