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.

IF 4.3 2区 医学 Q1 INFECTIOUS DISEASES Antibiotics-Basel Pub Date : 2024-12-04 DOI:10.3390/antibiotics13121171
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
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Abstract

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.

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叶绿醇抗多重耐药(MDR)菌株的增药活性、吸收、分布、代谢和排泄(ADME)及分子对接特性分析
背景:叶绿醇是一种来自长链不饱和无环醇的二萜,以其多种生物效应而闻名,包括抗菌和抗炎活性。叶绿醇存在于精油中,在制药和生物技术领域具有广泛的应用前景。本研究旨在评价叶绿醇对多药耐药菌的体外抗菌和增药作用,并评价其在硅片上的性能:ADME和分子对接。方法:采用微量稀释法对标准菌株和耐药菌株进行体外抑菌活性评价。最后,采用SwissADME平台分析叶绿醇的理化和药动学特性。结果:叶绿醇显著降低了诺氟沙星和庆大霉素抑制多重耐药菌株所需的最低抑制浓度(MIC),分别为大肠杆菌和金黄色葡萄球菌。此外,ADME分析显示,叶绿醇具有低毒性和良好的药代动力学特性;此外,通过分子对接发现叶绿醇与蛋白6GJ1和5KDR具有相关亲和力,但其亲和力低于庆大霉素和氨苄西林。结论:总的来说,这些发现表明叶绿醇有潜力作为对抗抗菌素耐药性的有效佐剂。
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来源期刊
Antibiotics-Basel
Antibiotics-Basel Pharmacology, Toxicology and Pharmaceutics-General Pharmacology, Toxicology and Pharmaceutics
CiteScore
7.30
自引率
14.60%
发文量
1547
审稿时长
11 weeks
期刊介绍: Antibiotics (ISSN 2079-6382) is an open access, peer reviewed journal on all aspects of antibiotics. Antibiotics is a multi-disciplinary journal encompassing the general fields of biochemistry, chemistry, genetics, microbiology and pharmacology. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. Therefore, there is no restriction on the length of papers.
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