Antimicrobial Activity of 4-Chlorocinnamic Acid Derivatives

Abstract

The microbial resistance of fungi and bacteria is currently considered a major public health problem. Esters derived from cinnamic acid have a broad spectrum of pharmacological properties that include antimicrobial activity. In this study, a collection of structurally related 4-chlorocinnamic acid esters was prepared using Fischer esterification reactions, alkyl or aryl halide esterification, and Mitsunobu and Steglich reactions. All of the esters were submitted to antimicrobial tests against strains of the species Candida albicans, Candida glabrata, Candida krusei, Candida guilliermondii, Pseudomonas aeruginosa, and Staphylococcus aureus. The compounds also were subjected to molecular docking study with the enzyme 14α-demethylase. Twelve esters derived from 4-chlorocinnamic acid were obtained, with yields varying from 26.3% to 97.6%, three of which were unpublished. The ester methyl 4-chlorocinnamate (1) presented activity against S. aureus at the highest concentration tested. In the antifungal evaluation, all of the esters were bioactive, but methoxyethyl 4-chlorocinnamate (4) and perillyl 4-chlorocinnamate (11) were the most potent (MIC = 0.13 and 0.024 μmol/mL, respectively). The data of molecular docking suggested that all the compounds present good affinity towards the active site related to antifungal activity. Therefore, the esters tested may be inhibitors of the enzyme 14α-demethylase. In addition, the results demonstrate that substituents of short alkyl chains with presence of heteroatom, such as oxygen, or those with a perillyl type terpenic substructure promote better antifungal profiles.

Synthetic Cinnamides and Cinnamates: Antimicrobial Activity, Mechanism of Action, and In Silico Study

“…compound 9 (decyl cinnamate) was bioactive against all Candida strains, with an MIC = 1101.92 µM, corroborating the results of a previous study [ 78 ] that reported on decyl 4-chlorocinnamate with antifungal action against strains of C. albicans ATCC 90028, C. glabrata ATCC 90030, C. krusei ATCC 34125, and C. guilliermondii ATCC 22017 (MIC = 3.10 μmol/mL, 3.10 μmol/mL, 3.10 μmol/mL, and 1.15 μmol/mL, respectively), evidencing the contribution of the decyl group in cinnamate analogs to the antifungal action.…”

“…When studying cell wall architecture, protoplasts stabilized with osmo-protectants are important biochemical tools [ 76 ]. Osmotic stability is used with C. albicans and other fungi to study antibiotic mechanisms of action [ 76 , 77 , 78 ]. Damage to essential components of the cell wall, caused by antifungal agents such as cell wall synthesis inhibitors, can lyse cells in the absence of an osmo-protectant.…”

Antileishmanial Activity of Cinnamic Acid Derivatives against Leishmania infantum

“…The compounds were obtained using three different methods: Fisher’s esterification [ 23 , 24 ], esterification with alkyl and aryl halides [ 25 , 26 ], and the Schotten–Baumann reaction using cinnamoyl chloride and differing though structurally related alcohols or amines, with pyridine [ 27 , 28 ] ( Scheme 1 ). Yields for the thirty-four derivatives ranged from 38% to 91.3%.…”

Effects of Microencapsulated Ferulic Acid or Its Prodrug Methyl Ferulate on Neuroinflammation Induced by Muramyl Dipeptide

“…The synthesis of Fer-Me and Caf-Me were carried out via Fischer esterification (described in Section 2.2 ) following a well-known procedure from literature, which gave the desired products in high yields (about 75%) [ 32 , 33 ]. In general, Fischer esterification is a very simple and low-cost one-pot reaction, with low environmental impact in terms of waste products and harmfulness of the reagents, compared to other methods, such as esterification via acyl-chloride.…”