Síntese e estudo de atividade antimicrobiana de ésteres inéditos obtidos a partir de ácidos cinâmicos e terpenos

Abstract

Antimicrobial resistance is a recurrent and gradual public health problem that hinders the treatment of bacteria, fungi, and other parasites. This situation has been driving researches aiming at the development of substances with antimicrobial action such as cinnamic acids and terpenes. In this context, the present work aims at the synthesis of novel ester compounds from the reaction between cinnamic acids derivatives with eugenol, thymol, carvacrol, and isoeugenol, using the molecular hybridization process, characterized by the junction of molecules with proven biological activities to produce another molecule with enhanced action. The esters were obtained through Steglich's esterification reaction, a simple and efficient route, with yields of around 80%. The synthesis took place in the following steps: Reaction of 6,7-dimethoxy-trans-cinnamic acid with the terpenes carvacrol, thymol, eugenol, and isoeugenol; and of 6,7- methylenedioxy-trans-cinnamic acid with carvacrol; in DCC (N,N'- Dicyclohexylcarbodiimide), DMAP (4-dimethylaminopyridine) and dichloromethane, under magnetic stirring and at room temperature. The following products were obtained: (E)-15-isopropyl-12-methylphenyl-4-(benzo-6,7-dioxol-2-yl) acrylate (7a), with a yield of 69.2%; (E)-4-(6,7-dimethoxyphenyl)-12-(13-methyl-16-isopropylphenyl) acrylate (9a), yield 76.1%, (E)-4-(6,7-dimethoxyphenyl)-12-(13-isopropyl-16- methylphenyl) acrylate (9b), yield 81.2%; (E)-15-allyl-13-methoxyphenyl-4-(6,7- dimethoxyphenyl) acrylate (9c), yield 84.9 % and (E)-13-methoxy-15-(E)-19- propenylphenyl-4-(6,7-dimethoxyphenyl) acrylate (9d), yield 82.1 %. The resulting compounds were identified employing IR, 1H NMR, and 13C NMR spectroscopic techniques (one- and two-dimensional). Subsequently, the antimicrobial activity against yeast and pathogenic bacterial species was investigated. Among the compounds evaluated, the (E)-15-isopropyl-12-methylphenyl-4-(benzo-6, 7-dioxol-2- yl) acrylate (7a) showed strong fungistatic activity against Candida albicans strains, however, without demonstrating such activity against non-albicans Candida strains. The other products examined did not show antimicrobial activity against the tested strains.