Synthesis, In Vitro Antimicrobial and In Silico Studies of Aminoalkyl Derivatives of Carvacrol

The global rise of antimicrobial resistance has created an urgent need for the development of new antimicrobial agents. Carvacrol, a natural phenolic compound, has drawn significant attention in medicinal chemistry due to its broad-spectrum biological activities. In the present study, two novel aminoalkyl derivatives of carvacrol were successfully synthesized through a Mannich-type reaction, which involves the condensation of carvacrol with formaldehyde and a secondary amine (dimethylamine or piperdine). Structural confirmation of the synthesized derivatives was carried out using spectroscopic techniques (1H-NMR and 13C-NMR). Based on the spectral data, the compounds were identified as 4-((dimethylamino)methyl)-5-isopropyl-2- methylphenol (2) and 5-isopropyl-2-methyl-4-(piperidin-1-ylmethyl)phenol (3). These compounds were evaluated for their in vitro antimicrobial activity against twenty-six bacterial strains and four fungal strains by using disc diffusion and broth dilution methods. Both compound 2 and 3 demonstrated a broad antimicrobial activity. Specifically, Compound 3 exhibited the highest antibacterial activity against Escherichia coli and Vibrio cholerae strains with a lower MIC value (25 µg/mL) and also showed superior antifungal activity against Candida albicans and Penicillium funiculosum NCTC 287 (MIC: 200 µg/mL). Furthermore, both compounds were evaluated through in silico studies to predict their potential mechanisms of action and assess their drug-likeness properties. Among the two, compound 2 exhibited the strongest binding affinity, with a docking score of -5.677kJ/mol against the target protein enoyl- acyl carrier protein reductase (FabI), a crucial enzyme in bacterial fatty acid biosynthesis. This work suggests that the aminoalkyl derivatives of carvacrol could be promising candidates for the development of new antimicrobial drugs that combat infections and help combat antimicrobial resistance.