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
Affiliations
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
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
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
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
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
Shellygton Lima Silva
Program of Natural and Synthetic Bioactive Products (PgPNSB), Health Sciences Center, Federal University of Paraíba, João Pessoa 58051-900, PB, Brazil
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
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
Valnês da Silva Rodrigues Junior
National Institute of Science and Technology in Tuberculosis (INCT-TB), Porto Alegre 90619-900, RS, Brazil
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
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
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.
