Antimicrobial Potential of Betulinic Acid and Investigation of the Mechanism of Action against Nuclear and Metabolic Enzymes with Molecular Modeling

Gabriela Cristina Soares Rodrigues; Mayara dos Santos Maia; Thalisson Amorim de Souza; Edeltrudes de Oliveira Lima; Luiz Eduardo Carneiro Gomes dos Santos; Shellygton Lima Silva; Marcelo Sobral da Silva; José Maria Barbosa Filho; Valnês da Silva Rodrigues Junior; Luciana Scotti; Marcus Tullius Scotti

doi:10.3390/pathogens12030449

journal article Open Access Mar 13, 2023

Antimicrobial Potential of Betulinic Acid and Investigation of the Mechanism of Action against Nuclear and Metabolic Enzymes with Molecular Modeling

Gabriela Cristina Soares Rodrigues

Mayara dos Santos Maia

Thalisson Amorim de Souza

Edeltrudes de Oliveira Lima Luiz Eduardo Carneiro Gomes dos Santos Shellygton Lima Silva Marcelo Sobral da Silva

José Maria Barbosa Filho Valnês da Silva Rodrigues Junior

Luciana Scotti

Marcus Tullius Scotti

Pathogens Vol. 12 No. 3 pp. 449 · MDPI AG

View at Publisher Save 10.3390/pathogens12030449

Abstract

Natural products have important pharmacological activities. This study sought to investigate the activity of the compound betulinic acid (BA) against different strains of bacteria and fungi. The minimum inhibitory concentration (MIC) was determined and then the minimum bactericidal concentration (MBC) and minimum fungicidal concentration (MFC). After performing the in vitro tests, molecular modeling studies were carried out to investigate the mechanism of action of BA against the selected microorganisms. The results showed that BA inhibited the growth of microbial species. Among the 12 species (Staphylococcus aureus, S. epidermidis, Pseudomonas aeruginosa, Escherichia coli, Mycobacterium tuberculosis, Candida albicans, C. tropicalis, C. glabrata, Aspergillus flavus, Penicillium citrinum, Trichophyton rubrum, and Microsporum canis) investigated, 9 (75%) inhibited growth at a concentration of 561 µM and 1 at a concentration of 100 µM. In general, the MBC and MFC of the products were between 561 and 1122 μM. In silico studies showed that BA presented a mechanism of action against DNA gyrase and beta-lactamase targets for most of the bacteria investigated, while for fungi the mechanism of action was against sterol 14α-demethylase (CYP51) targets and dihydrofolate reductase (DHFR). We suggest that BA has antimicrobial activity against several species.

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Details

Published: Mar 13, 2023
Vol/Issue: 12(3)
Pages: 449
License: View

Authors

G

Gabriela Cristina Soares Rodrigues

Laboratory of Cheminformatics, Program of Natural and Synthetic Bioactive Products (PgPNSB), Health Sciences Center, Federal University of Paraíba, João Pessoa 58051-900, PB, Brazil

M

Mayara dos Santos Maia

Laboratory of Cheminformatics, Program of Natural and Synthetic Bioactive Products (PgPNSB), Health Sciences Center, Federal University of Paraíba, João Pessoa 58051-900, PB, Brazil

T

Thalisson Amorim de Souza

Multi-User Characterization and Analysis Laboratory, Program of Natural and Synthetic Bioactive Products (PgPNSB), Health Sciences Center, Federal University of Paraíba, João Pessoa 58051-900, PB, Brazil

E

Edeltrudes de Oliveira Lima

Program of Natural and Synthetic Bioactive Products (PgPNSB), Health Sciences Center, Federal University of Paraíba, João Pessoa 58051-900, PB, Brazil

L

Luiz Eduardo Carneiro Gomes dos Santos

Program of Natural and Synthetic Bioactive Products (PgPNSB), Health Sciences Center, Federal University of Paraíba, João Pessoa 58051-900, PB, Brazil

S

Shellygton Lima Silva

Program of Natural and Synthetic Bioactive Products (PgPNSB), Health Sciences Center, Federal University of Paraíba, João Pessoa 58051-900, PB, Brazil

M

Marcelo Sobral da Silva

Multi-User Characterization and Analysis Laboratory, Program of Natural and Synthetic Bioactive Products (PgPNSB), Health Sciences Center, Federal University of Paraíba, João Pessoa 58051-900, PB, Brazil

J

José Maria Barbosa Filho

Multi-User Characterization and Analysis Laboratory, Program of Natural and Synthetic Bioactive Products (PgPNSB), Health Sciences Center, Federal University of Paraíba, João Pessoa 58051-900, PB, Brazil

V

Valnês da Silva Rodrigues Junior

National Institute of Science and Technology in Tuberculosis (INCT-TB), Porto Alegre 90619-900, RS, Brazil; Program of Biotechnology, Center for Biotechnology, Federal University of Paraíba, Campus I, Cidade Universitária, João Pessoa 58051-900, PB, Brazil

L

Luciana Scotti

Laboratory of Cheminformatics, Program of Natural and Synthetic Bioactive Products (PgPNSB), Health Sciences Center, Federal University of Paraíba, João Pessoa 58051-900, PB, Brazil

M

Marcus Tullius Scotti

Laboratory of Cheminformatics, Program of Natural and Synthetic Bioactive Products (PgPNSB), Health Sciences Center, Federal University of Paraíba, João Pessoa 58051-900, PB, Brazil

Funding

Coordination for the Improvement of Higher Education Personnel—Brazil (CAPES) Award: Financing Code 001

Cite This Article

Gabriela Cristina Soares Rodrigues, Mayara dos Santos Maia, Thalisson Amorim de Souza, et al. (2023). Antimicrobial Potential of Betulinic Acid and Investigation of the Mechanism of Action against Nuclear and Metabolic Enzymes with Molecular Modeling. Pathogens, 12(3), 449. https://doi.org/10.3390/pathogens12030449

Antimicrobial Potential of Betulinic Acid and Investigation of the Mechanism of Action against Nuclear and Metabolic Enzymes with Molecular Modeling

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