Antimicrobial and antioxidant activities of amines derived from vanillin as potential preservatives: Impact of the substituent chain length and polarity

Abstract

The stability of cosmetic products in terms of microbial safety or oxidation is a major challenge when faced with consumer's expectations for less controversial compounds used in their formulation. In this context, we present new vanillin derivatives synthesized in a two steps one-pot process. The synthesis was based on the reductive amination reaction between vanillin and a selected panel of amines with different structural units such as alkyl chains, halogens and aromatics. The different molecules were designed to bring a better understanding of the structure-preservative activity relationships in vanillin-based molecules. Most compounds exhibited strong antioxidant activities in DPPH, ABTS and FRAP assays. The antibacterial and antifungal properties were evaluated on several strains known to be responsible for the contamination of cosmetic products. Some of these vanillin compounds derived with a p-ethylaniline (2c), with a p-butylaniline (2d), with a p-hexylaniline (2e) and a p-iodoaniline (3b) showed a promising level of antibacterial activity against Bacillus subtilis and Micrococcus luteus. In particular, 2d was very active against most of the tested bacterial and fungal strains and showed very promising antibacterial and antifungal capabilities while displaying among the highest antioxidant capacity and no cytotoxic effect on human fibroblasts. We investigated if a correlation between the hydrophobicity and biological activities of the compounds could be established and we highlighted that the presence of aliphatic chains grafted on the aromatic amine ring is associated to the highest antimicrobial activities. The structure-activity relationships highlighted in this study allow paving the way for future applications of these compounds in cosmetics as alternative to controversial molecules.