Anti-inflammatory and anti-allergic activity of Jacareubin derivatives

Abstract Xanthone Jacareubin (JAC) isolated from heartwood of Calophyllum brasiliense has shown good anti-inflammatory against spike protein of SARS-CoV2 and anti-allergic activity. Methoxylated (Met) and acetylated (Ac) derivatives of JAC and its precursor xanthone V (X-V) were analyzed in this work to identify the structural functional groups that confer their biological activity. Met- and Ac-derivatives of JAC and X-V were synthesized and identified by 1H and 13C-NMR and MS. All compounds were evaluated for β-hexosaminidase degranulation (β-hex) of Bone Marrow Mast Cells. Both xanthones and Met-JAC derivative (3metJac) were evaluated on their inhibitory activity of xanthine oxidase (XO) and inhibition of passive cutaneous anaphylaxis (PCA). Also, both xanthones, 3metJac, and 4AcX-V were evaluated for inhibitory activity of Myeloperoxidase (MPO) and TPA-induced edema in mice. JAC showed better inhibition of β-hex than X-V, while Met-derivatives showed greater inhibitory activity on β-hex than JAC and X-V, but Ac-derivatives showed reduced inhibitory activity. Inhibition of XO and MPO of both xanthones showed the highest activity at 1 μmol/ear compared to Met- and Ac-derivatives evaluated. Also, both xanthones showed higher anti-inflammatory activity in the TPA-induced edema compared to the Met- and Ac-derivatives. While in the PCA, JAC and 3metJac showed similar inhibition and twice the inhibition of X-V and their derivatives. These results suggest that the fourth ring in the JAC is an important structural group for anti-allergic activity because X-V does not possess the fourth cyclized ring and has a fourth hydroxyl substituent group, showing poor inhibition of the allergic response. Supported by Conacyt Grant CF-2019-51488. Supported by Conacyt Grant CF-2019-51488