A one-pot and eco-friendly synthesis of novel β-substituted-α-halomethyl acrylates and the bioactivity of these compounds in an in vitro model of mast cell degranulation induced by pro-inflammatory stimuli

Abstract

The goal of the present work was to develop novel β-substituted-α-halomethyl acrylates from a methodology in an aqueous phase and to evaluate their bioactivity as potential inhibitors of mast cell activation. Eleven β-substituted-α-halomethyl acrylates were synthesized through a modified Horner-Wadsworth-Emmons reaction. Compound 48/80 and the calcium ionophore A23187 stimulated the release of β-hexosaminidase from mast cells. The effect induced by compound 48/80 was inhibited by compound 5 (320 µM) and compound 9 (160 and 320 µM) without causing cytotoxic effects. The effect induced by A23187 was inhibited by compound 5 (40, 80, 160, and 320 µM) without affecting cell viability. The inhibitory effects exhibited by compounds 5 and 9 were more potent than those of the reference compound sodium cromoglycate at the same concentrations. The biochemical results were consistent with the morphological findings obtained by light and transmission electron microscopy. This study reports, for the first time, that the new synthetic compounds methyl (Z)− 2-bromo-3-(furan-3-yl)acrylate (compound 5) and methyl (E)− 2-bromo-3-(3-bromophenyl)acrylate (compound 9) strongly inhibit mast cell degranulation, without affecting cell viability. The implications of these results are relevant as a basis for developing new anti-inflammatory and mast cell stabilizing drugs.

Keywords

• Horner-Wadsworth-Emmons reaction
• Mast cells
• Compound 48/80
• Calcium ionophore A23187
• β-hexosaminidase
• Degranulation