Antimicrobial, synergistic and antibiofilm activities of Myristica fragrans Houtt. Bioactive compounds and their derivatives

This study investigates the antimicrobial efficacy, synergistic interactions, antibiofilm activity, molecular docking studies, and drug-likeness properties of α-terpineol, 4-carvomenthenol, and their derivatives isolated from nutmeg and mace (Myristica fragrans Houtt.). α-Terpineol and 4-carvomenthenol were isolated from nutmeg essential oil and mace oleoresin respectively using column chromatography. Derivatization of α-Terpineol was derivatized into its ester, epoxide, ether, and allylic bromide while 4-carvomenthenol was derivatized to form its ester and epoxide. The antimicrobial activity of isolated compounds and their derivatives was assessed against Bacillus sp., Staphylococcus aureus, Yersinia enterocolitica and Escherichia coli followed by testing of their synergistic interactions with streptomycin. Additionally, the antibiofilm activity of the most effective treatments alone and in combination with was tested in combination with streptomycin was also evaluated. Molecular docking studies were conducted to assess binding affinities of the most effective treatments for DNA gyrase and transpeptidase followed byADMET profiling to evaluate their drug-likeness. The ester derivatives of α-terpineol and 4-carvomenthenol demonstrated the highest antibacterial potential with MIC values ranging from 40 to 170 µg/ml. Both the ester derivatives showed significant synergistic interactions with streptomycin and exhibited strong to intermediate antibiofilm activity against all the tested bacteria. Molecular docking studies indicated favorable binding affinities (-6.56 to - 4.31 kcal/mol) of ester derivatives for DNA gyrase and transpeptidase as compared to their parent compounds having favorable physicochemical properties, meeting drug-likeness criteria. α-Terpineol ester and 4-carvomenthenol ester exhibited promising antimicrobial potential, synergistic interaction with streptomycin and antibiofilm properties, suggesting their potential as novel therapeutic agents. Further development and investigation of these compounds are warranted to explore their applications in clinical settings.