Biocatalytic synthesis, toxicity studies and antimicrobial properties against bacteria and fungi of arginine-based surfactants

FAIT, M.E.; DA COSTA, H.P.S.; DO SANTOS QUEIROZ, A.; LORENZO, J.; GARROTE, G.L.; MORCELLE, S.R.

Congreso; 4º Reunión Internacional de Ciencias Farmacéuticas (RICIFA); 2016

Two novel arginine-based cationic surfactants, Nα-benzoyl-arginine decylamide (Bz-Arg-NHC10) and Nα-benzoyl-arginine dodecyl amide (Bz-Arg-NHC12), were synthesized using papain (an endopeptidase from Carica papaya latex) adsorbed onto polyamide as biocatalyst. Nα-benzoyl-arginine ethyl ester hydrochloride (the classical substrate for the determination of cysteine and serine proteases activity) was used as arginine donor, whereas decyl- and dodecylamine were used as nucleophiles for the condensation reaction, with yields higher than 80%. The purification process was achieved by a single cationic exchange chromatographic separation, involving the use of water and ethanol as the main separation solvents. Bz-Arg-NHC10 and Bz-Arg-NHC12 proved antimicrobial activity against both Gram-positive and Gram-negative bacteria, revealing their potential use as effective disinfectants, as they reduced 99% the initial bacterial population after only 1 h of contact. The cytotoxic effect towards different cell types of both arginine derivatives was also investigated. Bz-Arg-NHCn demonstrated lower hemolytic activity and were less eye-irritating than the commercial cationic surfactant Cetrimide. A similar trend could also be observed when cytotoxicity was tested on hepatocytes and fibroblast cell lines: both arginine derivatives were less toxic than Cetrimide. Antifungal studies revealed all three cationic compounds were capable of inhibiting microconidia germination of two Trichophyton species, showing similar fungistatic efficacy. Finally, Bz-Arg-NHCn also demonstrated fungistatic activity against Candida albicans (a yeast that can develop a filamentous form), and Bz-Arg-NHC10 had also a fungicidal effect against this pathogen. In this case, two strains of C. albicans (an ATTC and a clinical isolate) were tested, being the MIC and MFC values higher for the clinical isolate than for the ATCC strain. Overall, the evidence from this preliminary study supports the use of these arginine-based surfactants as a promising alternative to commercial cationic surfactants, especially for their use as additives in topical formulations.