Analysis of the Antibiotic-Potentiating Activity, Absorption, Distribution, Metabolism, and Excretion (ADME) and the Molecular Docking Properties of Phytol Against Multi-Drug-Resistant (MDR) Strains
José Weverton Almeida-Bezerra,
Saulo Almeida Menezes,
José Thyálisson da Costa Silva,
Simone Galdino de Sousa,
Daniel Sampaio Alves,
Gabriel Gonçalves Alencar,
Isaac Moura Araújo,
Ewerton Yago de Sousa Rodrigues,
Cícera Datiane de Morais Oliveira-Tintino,
Rafael Pereira da Cruz,
Janaína Esmeraldo Rocha,
Saulo Relison Tintino,
José Maria Barbosa-Filho,
Maria Flaviana Bezerra Morais-Braga,
Irwin Rose Alencar de Menezes,
António Raposo,
Henrique Douglas Melo Coutinho
Affiliations
José Weverton Almeida-Bezerra
Department of Biological Chemistry, Regional University of Cariri—URCA, Crato 63105-000, CE, Brazil
Saulo Almeida Menezes
Biotechnology Center, Federal University of Rio Grande do Sul—UFRGS, Porto Alegre 91501-970, RS, Brazil
José Thyálisson da Costa Silva
Department of Biological Sciences, Regional University of Cariri—URCA, Crato 63105-000, CE, Brazil
Simone Galdino de Sousa
Department of Biological Sciences, Regional University of Cariri—URCA, Crato 63105-000, CE, Brazil
Daniel Sampaio Alves
Department of Biological Sciences, Regional University of Cariri—URCA, Crato 63105-000, CE, Brazil
Gabriel Gonçalves Alencar
Department of Biological Sciences, Regional University of Cariri—URCA, Crato 63105-000, CE, Brazil
Isaac Moura Araújo
Department of Biological Chemistry, Regional University of Cariri—URCA, Crato 63105-000, CE, Brazil
Ewerton Yago de Sousa Rodrigues
Department of Biological Sciences, Regional University of Cariri—URCA, Crato 63105-000, CE, Brazil
Cícera Datiane de Morais Oliveira-Tintino
Department of Biological Chemistry, Regional University of Cariri—URCA, Crato 63105-000, CE, Brazil
Rafael Pereira da Cruz
Department of Biological Sciences, Regional University of Cariri—URCA, Crato 63105-000, CE, Brazil
Janaína Esmeraldo Rocha
Center of Science and Technology CCT, State University of Ceara—UECE, Fortaleza 63100-000, CE, Brazil
Saulo Relison Tintino
Department of Biological Sciences, Regional University of Cariri—URCA, Crato 63105-000, CE, Brazil
José Maria Barbosa-Filho
Department of Pharmacy, Federal University of Paraíba—UFPB, João Pessoa 58059-900, PB, Brazil
Maria Flaviana Bezerra Morais-Braga
Department of Biological Sciences, Regional University of Cariri—URCA, Crato 63105-000, CE, Brazil
Irwin Rose Alencar de Menezes
Department of Biological Chemistry, Regional University of Cariri—URCA, Crato 63105-000, CE, Brazil
António Raposo
CBIOS (Research Center for Biosciences and Health Technologies), Universidade Lusófona de Humanidades e Tecnologias, Campo Grande 376, 1749-024 Lisboa, Portugal
Henrique Douglas Melo Coutinho
Department of Biological Chemistry, Regional University of Cariri—URCA, Crato 63105-000, CE, Brazil
Background: Phytol is a diterpene from the long-chain unsaturated acyclic alcohols, known for its diverse biological effects, including antimicrobial and anti-inflammatory activities. Present in essential oils, phytol is a promising candidate for various applications in the pharmaceutical and biotechnological sectors. This study aimed to evaluate the in vitro antibacterial and drug-potentiating effects of phytol against multidrug-resistant bacteria and to evaluate its in silico properties: ADME and molecular docking. Methods: The in vitro antibacterial activity of phytol and the phytol combined with conventional drugs was evaluated by microdilution tests against standard and resistant bacterial strains. Finally, the SwissADME platform was employed to analyse the physicochemical and pharmacokinetic characteristics of phytol. Results: Phytol significantly reduced the Minimum Inhibitory Concentration (MIC) of norfloxacin and gentamicin required to inhibit multidrug-resistant strains of Escherichia coli and Staphylococcus aureus, respectively. Additionally, ADME analysis revealed that phytol exhibits low toxicity and favourable pharmacokinetic properties; in addition, it is revealed through molecular docking that phytol showed a relevant affinity with the proteins 6GJ1 and 5KDR, however, with values lower than the drugs gentamicin and ampicillin. Conclusions: Collectively, these findings suggest that phytol holds potential as an effective adjuvant in combating antimicrobial resistance.
