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Identification of Phytochemicals with Inhibitory Potential Against Beta-lactamase Enzymes via Computer-aided Approach.
Nwokebu, Goodness Chizorom; Adesina, Abdurahman Babatunde; Isibor, Clement Ndudi; Aigbepue, Stephen Ayaosi; Egbo, Chidinma Confidence; Pureaziba, Nelson; Isaac, Opeyemi Oluwafemi; Owolade, Adedoyin John-Joy; Alabere, Hafsat Olateju; Iwuagwu, Mary Oluchi; Hussein, Mutiat Olamide; Ibrahim, Abdulwasiu; Balogun, Toheeb Adewale.
Afiliação
  • Nwokebu GC; Department of Pharmaceutical and Medicinal Chemistry, University of Nigeria, Nsukka, Enugu State, Nigeria; Institute of Bioinformatics and Molecular Therapeutics, Oshogbo, Osun State, Nigeria.
  • Adesina AB; Institute of Bioinformatics and Molecular Therapeutics, Oshogbo, Osun State, Nigeria; Department of Veterinary Public Health and Preventive Medicine, Usmanu Danfodiyo University, Sokoto, Nigeria.
  • Isibor CN; Institute of Bioinformatics and Molecular Therapeutics, Oshogbo, Osun State, Nigeria; Department of Biological Sciences, University of Delta, Agbor, Delta State, Nigeria.
  • Aigbepue SA; Institute of Bioinformatics and Molecular Therapeutics, Oshogbo, Osun State, Nigeria; Department of Pharmacology and Therapeutics, University of Ibadan, Nigeria.
  • Egbo CC; Institute of Bioinformatics and Molecular Therapeutics, Oshogbo, Osun State, Nigeria; Department of Pharmaceutical and Medicinal Chemistry, University of Nigeria, Nsukka, Nigeria.
  • Pureaziba N; Institute of Bioinformatics and Molecular Therapeutics, Oshogbo, Osun State, Nigeria; Department of Microbiology, Niger Delta University, Delta State, Nigeria.
  • Isaac OO; Institute of Bioinformatics and Molecular Therapeutics, Oshogbo, Osun State, Nigeria; Department of Chemistry, Adekunle Ajasin University, Akungba-Akoko, Ondo State, Nigeria.
  • Owolade AJ; Institute of Bioinformatics and Molecular Therapeutics, Oshogbo, Osun State, Nigeria; Faculty of Pharmacy, Obafemi Awolowo University, Ile Ife, Osun State, Nigeria.
  • Alabere HO; Institute of Bioinformatics and Molecular Therapeutics, Oshogbo, Osun State, Nigeria; Department of Life Sciences, Aberystwyth University, United Kingdom.
  • Iwuagwu MO; Institute of Bioinformatics and Molecular Therapeutics, Oshogbo, Osun State, Nigeria; Department of Plant Science and Biotechnology, Abia State University, Uturu, Abia State, Nigeria.
  • Hussein MO; Institute of Bioinformatics and Molecular Therapeutics, Oshogbo, Osun State, Nigeria; Biology Unit, Department of Biological Sciences, Usmanu Danfodiyo University, Sokoto, Nigeria.
  • Ibrahim A; Institute of Bioinformatics and Molecular Therapeutics, Oshogbo, Osun State, Nigeria; Department of Biochemistry and Molecular Biology, Usmanu Danfodiyo University, Sokoto, Nigeria; Kwara Emerging Scholars Forum, Ilorin, Kwara State, Nigeria. Electronic address: Ibrahimabdulwasiu44@gmail.com.
  • Balogun TA; Institute of Bioinformatics and Molecular Therapeutics, Oshogbo, Osun State, Nigeria.
Bioorg Chem ; 145: 107238, 2024 Apr.
Article em En | MEDLINE | ID: mdl-38412652
ABSTRACT

INTRODUCTION:

Antibacterial drugs have been widely used for the past century to treat diseases, but their efficacy has been limited by multi-resistant pathogens, particularly those that utilize beta-lactamase enzymes. The inhibition of beta-lactamase enzymes holds great promise for reducing the influence of such pathogens.

OBJECTIVE:

This study aims to evaluate the mechanism of inhibition of phytochemicals with antibacterial activity against two classes of beta-lactamases using computational methods.

METHODS:

To achieve this objective, a total of thirty phytochemicals were docked against SHV-1 beta-lactamase and AmpC beta-lactamase after procurement from Protein Data Bank. The pharmacokinetics (ADMET) and density functional theory (DFT) analysis study were also conducted to unravel the nature of the top six most promising compounds on each protein.

RESULTS:

The results showed that a significant percentage of the compounds had binding affinities greater than that of avibactam, the positive control. Quercetin-3-O-rutinoside showed the most promising results against SHV-1 beta-lactamase with an affinity of -9.4 kcal/mol, while luteolin was found to be the most promising candidate against AmpC beta-lactamase with an affinity of -8.5 kcal/mol. DFT analysis demonstrated the reactivity of these compounds, and the ADMET study indicated that they were relatively safe.

CONCLUSION:

In conclusion, the study's findings suggest that the selected compounds have significant potential to inhibit beta-lactamase and may be used in combination with antibiotics against organisms that produce beta-lactamase. This study provides a basis for further research in a wet-lab setting to validate the results.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Beta-Lactamases / Inibidores de beta-Lactamases Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Beta-Lactamases / Inibidores de beta-Lactamases Idioma: En Ano de publicação: 2024 Tipo de documento: Article