Derivados sintéticos do ácido 4-clorocinâmico e atividade antimicrobiana

Abstract

Currently the microbial resistance of fungi and bacteria is considered a major public health problem. The term candidiasis is used for superficial or systemic opportunistic infections caused by different species of the genus Candida. Individuals with HIV, chronic diseases such as cancer, diabetes and transplanted patients, because they are immunocompromised patients, as well as the elderly and newborns are the groups with the greatest predisposition to these infections. Some of the species of this genus have shown resistance to a wide range of antifungal drugs, increasing the severity of these infections and the complexity of their treatment. Esters derived from cinnamic acid have a broad spectrum of pharmacological activities, including antimicrobial activity. It is reported that chlorinated cinnamic esters are potentially bioactive against microorganisms. Thus, the objective of this work was to prepare a collection of structurally related 4-chlorocinnamic acid esters, to evaluate the antimicrobial activity of the same, and to establish a relationship between the structure and biological activity of these compounds. For ester preparation, Fischer esterification reactions, esterification using alkyl and aryl halides, Mitsunobu reaction and Steglich reaction were used. Spectroscopic infrared (IR) and 1H and 13C nuclear magnetic resonance methods, including high resolution mass spectrometry for the unpublished ester, were used in the characterization of the products. All the esters were submitted to antimicrobial tests against strains of Candida albicans, Candida glabrata, Candida krusei, Candida guilliermondii, Pseudomonas aeruginosa and Staphylococcus aureus, using the microdilution method in broth, having as antimicrobial control chloramphenicol and nystatin. There were obtained twelve esters derived from 4-chlorocinnamic acid, whose yields ranged from 26.3% - 97.6%, three of which were unpublished. An ester presented antibacterial activity in the highest concentration tested, however, in the antifungal activity all the compounds were bioactive. In the antifungal activity esters that stood out RH-06 and RH-11 presented MIC 0.13 and 0.024 μmol/mL, respectively. These results show that the substituents of short alkyl chains, with presence of heteroatom like oxygen or with terpenic substructure of the perilic type, present better antifungal profile.