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

• Published in: Biomedicine & pharmacotherapy 2024-01, Vol.170, p.116009-116009, Article 116009
• Main Authors: Martínez, Maricel, Mariani, María Laura, García, Celina, Ceñal, Juan Pedro, Penissi, Alicia Beatriz
• Format: Article
• Language: English
• Subjects: Aqueous medium; Calcium ionophore A23187; Compound 48/80; Degranulation; Horner-Wadsworth-Emmons reaction; Mast cells; Methyl-β-substituted-α-halo acrylates; β-hexosaminidase
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2023.116009

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. [Display omitted] •β-substituted-α-halomethyl acrylates were obtained in aqueous medium.•Compounds 5 and 9 inhibited β-hexosaminidase release in the presence of compound 48/80 and the calcium ionophore A23187.•Microscopy analysis showed a lower degree of degranulation in cells treated with compounds 5 and 9.•The inhibitory effect of compounds 5 and 9 in the presence of compound 48/80 was higher than that exhibited by sodium cromoglycate.•The inhibitory effect of compound 5 in the presence of A23187 was higher than that of sodium cromoglycate.