N-[3-(Aminomethyl)‎benzyl]acetamidine (1400 W)‎ as a Potential Immunomodulatory Agent

Abstract EN

This study was designed to investigate the relationship between NO, IL-12, and TNF-α production by J774A.1 macrophages activated with LPS and IFN-γ in the presence of N-[3-(aminomethyl)benzyl]acetamidine (1400 W).

1400 W is a novel, highly selective inhibitor of inducible nitric oxide synthase (iNOS).

We compared the obtained data with the effect of NG-monomethyl-L-arginine (L-NMMA) (a nonselective NOS inhibitor) and L-NG-(1-iminoethyl)lysine (L-NIL) (a relatively selective inhibitor of iNOS activity) on cells in this model.

To investigate the involvement of an exogenous NO on IL-12 and TNF-α production we used NO donor—S-nitrosocaptopril (S-NO-Cap).

The most potent inhibitor of NO generation was 1400 W.

This compound also markedly increased IL-12 p40 secretion and decreased TNF-α release.

L-NIL suppressed both NO and TNF-α production, but it did not change IL-12 p40 synthesis.

The effect of L-NMMA on NO generation was weaker than other inhibitors.

Moreover, it decreased TNF-α secretion slightly but not significantly.

IL-12 p40 production by stimulated cells was inhibited by S-NO-Cap in a dose dependent manner, but no effect on TNF-α release was observed.

The potency and selectivity of 1400 W as an inhibitor of iNOS and cytokine release modifier are encouraging for therapeutic use.