Morita-Baylis-Hillman Adduct 2-(3-Hydroxy-2-oxoindolin-3-yl)acrylonitrile (ISACN) Modulates Inflammatory Process In vitro and In vivo.

ABSTRACT

Morita-Baylis-Hillman adducts (MBHA) are synthetic molecules with several biological actions already described in the literature. It has been previously described that adduct 2-(3-hydroxy-2-oxoindolin-3-yl)acrylonitrile (ISACN) has anticancer potential in leukemic cells. Inflammation is often associated with the development and progression of cancer. Therefore, to better understand the effect of ISACN, this study aimed to evaluate the anti-inflammatory potential of ISACN both in vitro and in vivo. Results demonstrated that ISACN negatively modulated the production of inflammatory cytokines IL-1ß, TNF-α, and IL-6 by cultured macrophages. In vivo, ISACN 6 and 24 mg/kg treatment promoted reduced leukocyte migration, especially neutrophils, to the peritoneal cavity of zymosan-challenged animals. ISACN displays no anti-edematogenic activity, but it was able to promote a significant reduction in the production of inflammatory cytokines in the peritoneal cavity. These data show, for the first time, that MBHA ISACN negatively modulates several aspects of the inflammatory response, such as cell migration and cytokine production in vivo and in vitro, thus having an anti-inflammatory potential.