Atividade Anti-Staphylococcus aureus Meticilina Resistente (MRSA) de um novo composto 3-Calcogenil Indol

Autores

DOI:

https://doi.org/10.15448/1980-6108.2021.1.41325

Palavras-chave:

anti-MRSA, chalcogenil-indóis, novos antimicrobianos, ensaios de curva de morte, Staphylococcus aureus

Resumo

Objetivo: o desenvolvimento de novos antimicrobianos contra Staphylococcus aureus resistentes à meticilina (MRSA) é uma prioridade para a Organização Mundial da Saúde. Então, o objetivo desse estudo foi avaliar a atividade antibacteriana e a toxicidade do 5-bromo-3-((4-metoxifenil) sulfenil)-1H-indol (3b) contra MRSA.
Métodos: a concentração inibitória minima de 3b foi determinada contra S. aureus ATCC 29213 e 43 isolados clínicos. O ensaio de curva de morte foi realizado para nove isolados. Análise de variância seguida pelo teste post hoc Bonferroni foi usada para testes estatísticos.
Resultados e conclusões: a MIC50 e MIC90 do 3b foi 4 μg.mL-1 e 16 μg.mL-1, respectivamente. No ensaio de curva de morte, o 3b demonstrou atividade bactericida contra todos os isolados avaliados na concentração de 1xMIC e 2xMIC e o recrescimento não foi observado. Em relação aos testes de toxicidade, 3b não apresentou citotoxicidade, mutagenicidade ou alergenicidade. 3b apresentou atividade particularmente interessante contra MRSA, demonstrando alto potencial para o desenvolvimento de novos produtos antimicrobianos.

Downloads

Não há dados estatísticos.

Biografia do Autor

Laisa Borges Ferreira, Federal University of Rio Grande do Sul (UFRGS).

Master in Agricultural and environmental Microbiology, Institute of Health Sciences, Federal University of Rio Grande do Sul (UFRGS), in Porto Alegre, RS, Brazil. Clinical Research coordinator at Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil.

Edilma Elayne da Silva, Federal University of Rio Grande do Sul (UFRGS).

Master in Chemistry, Federal University of Pernambuco, RE, Brazil. Doctorate Student in Organic chemistry, Institute of Chemistry (IQ), Federal University of Rio Grande do Sul (UFRGS), in Porto Alegre, RS, Brazil.

Silvia Adriana Meyer Lentz, Federal University of Rio Grande do Sul (UFRGS).

Master in Agricultural and Environmental Microbiology, Institute of Health Sciences, Federal University of Rio Grande do Sul (UFRGS), in Porto Alegre, RS, Brazil. Doctorate student at in Agricultural and Environmental Microbiology, Institute of Health Sciences, Federal University of Rio Grande do Sul (UFRGS), in Porto Alegre, RS, Brazil.

Juliano Braun de Azeredo, Federal University of Rio Grande do Sul (UFRGS).

PhD and Master in Organig Chemistry, Federal University of Santa Catarina (UFSC), in Florianópolis, SC, Brazil. Professor at Organic Chemistry and Pharmacognosy Laboratory, Federal University of Pampa (UNIPAMPA), in Uruguaiana, RS, Brazil.

Antonio Luiz Braga, Federal University of Rio Grande do Sul (UFRGS).

PhD and Master in Organig Chemistry, Federal University of São Paulo (UNIFESP), in São Paulo, SP, Brazil. Professor at Chemistry department, Federal University of Santa Catarina (UFSC), in Florianópolis, SC, Brazil.

Michel Mansur Machado, Federal University of Rio Grande do Sul (UFRGS).

PhD in Biological Science, Federal University of Santa Maria (UFSM), in Santa Maria, RS, Brazil. Master in Pharmaceutical Science, Federal University of Santa Maria (UFSM), in Santa Maria, RS, Brazil. Professor at Clinical Immunology and Toxicology Laboratory, Federal University of Pampa (UNIPAMPA), in Uruguaiana, RS, Brazil.

Mario Lettieri Teixeira, Federal University of Rio Grande do Sul (UFRGS).

PhD and Master in Molecular and Cellular Biology, Federal University of Rio Grande do Sul (UFRGS), in Porto Alegre, RS, Brazil. Professor at Federal Institute of Santa Catarina, in Concórdia, SC, Brazil.

Juliana Caierão, Federal University of Rio Grande do Sul (UFRGS).

PhD in Science, Federal University of Rio de Janeiro (UFRJ), in Rio de Janeiro, RJ, Brazil. Master in Medical Science, Federal University of Health Science of Porto Alegre, in Porto Alegre, RS, Brazil (UFCSPA). Professor at Postgraduate Program in Pharmaceutical Sciences, Federal University of Rio Grande do Sul, in Porto Alegre, RS, Brazil.

Gustavo Pozza Silveira, Federal University of Rio Grande do Sul (UFRGS).

Doctor in Chemistry, Federal University of Santa Catarina (UFSC), in Florianópolis, SC, Brazil. Professor at Federal University of Rio Grande do Sul (UFRGS), in Porto Alegre, RS, Brazil.

Andreza Francisco Martins, Federal University of Rio Grande do Sul (UFRGS).

Doctor in Medical Science, Federal University of Rio Grande do Sul (UFRGS), in Porto Alegre, RS, Brazil. Master in Pharmaceutical Science, Federal University of Rio Grande do Sul (UFRGS), in Porto Alegre, RS, Brazil. Professor at Federal University of Rio Grande do Sul (UFRGS), in Porto Alegre, RS, Brazil.

Referências

Word Heath Organization. Global priority list of antibiotic- resistant bacteria to guide research, discovery, and development of new antibiotics [Internet]; 2017 [cited 2017 Nov 20]. Available from: http://www.who.int/medicines/publications/global-prioty-list-antibiotic-resistant-bacteria

Moellering RC. Discovering new antimicrobial agents. Int J Antimicrob Agents. 2011;37(1):2-9. https://doi.org/10.1016/j.ijantimicag.2010.08.018

Welsch ME, Snyder, Stockwell BR. Privileged scaffolds for library design and drug Discovery. Curr Opin Chem Bio. 2010;14(3):347-61. https://doi.org/10.1016/j.cbpa.2010.02.018

Batista BG, Lana DFD, Silveira GP, Sá MM, Ferreira M, Russo TVC, et al. Allylic selenocyanate as new agents to combat Fusarium species involved with human infections. Chemistry Select. 2017;2(35):11926-32. https://doi.org/10.1002/slct.201702338

Azeredo JB, Godoi M, Martins GM, Silveira CC, Braga AL. A solvent- and metal-free synthesis of 3‑Chacogenyl- indoles employing DMSO/I2 as an eco-friendly catalytic oxidation system. J Org Chem. 2014;79(9):4125-50. https://doi.org/10.1021/jo5000779

Clinical and Laboratory Standards Institute (CLSI). Performance standards for antimicrobial susceptibility. Twenty-second Information Supplement. CLSI document M100-S25 [Internet]. Wayne, PA: Clinical and Laboratory Standards Institute; 2015 [updated 2018 Jan 24]. Available from: https://clsi.org/standards/products/free-resources/access-our-free-resources

Isenberg HD. Clinical Microbiology Procedures Handbook (American S). editor in chief. Washington, D.C: American Society of Microbiology; 1992. p. 12.

Montagner GFMS, Sagrillo M, Machado MM, Almeida RC, Mostardeiro CP, Duarte MMMF, et al. Toxicological effects of ultraviolet radiation on lymphocyte cells with different manganese superoxide dismutase Ala16Val polymorphism genotypes. Toxicology in Vitro. 2010;24(5):1410-6. https://doi.org/10.1016/j.tiv.2010.04.010

Burow ME, Weldon CB, Tang Y, et al. Differences in susceptibility to tumor necrosis factor α-induced apoptosis among MCF-7 breast cancer cell variants. Cancer Res. 1998;58(21):4940-6.

Singh NP, McCoy MT, Tice RR, Schneider EL. A simple technique for quantitation of low levels of DNA damage in individual cells. Exp Cell Res. 1988;175(1):184-91. https://doi.org/10.1016/0014-4827(88)90265-0

Jacobsen ID, Grosse K, Slesiona S, Hube B, Berndt A, Brock M. Embryonated eggs as an alternative infection model to investigate Aspergillus fumigatus virulence. Infect Immun. 2010;78(7):2995-3006. https://doi.org/10.1128/IAI.00268-10

Cruz-Muñiz MY, López-Jacome LE, Hernández-Durán M, Franco-Cendejas R, Licona-Limón P, Ramos-Balderas JL, et al. Repurposing the anticancer drug mitomycin C for the treatment of persistent Acinetobacter baumannii infections. Int J Antimicrob Agents. 2017;49(1):88-92. https://doi.org/10.1016/j.ijantimicag.2016.08.022

Li SA, Cadelis MM, Sue K, Blanchet M, Vidal N, Brunel JM, et al. 6-Bromoindolglyoxylamido derivatives as antimicrobial agents and antibiotic enhancers. Bioorg Medic Chem. 2019; 27(10):2090-9. https://doi.org/10.1016/j.bmc.2019.04.004

Daly S, Hayden K, Malik I, Porch N, Tang H, et al. Unprecedented C-2 arylation of indole with diazonium salts: Syntheses of 2,3-disubstituted indoles and their antimicrobial activity. Bioorg Med Chem Lett. 2011;21(16):4720-3. https://doi.org/10.1016/j.bmcl.2011.06.081

Sakhuja R, Panda SS, Khanna L, Khurana S, Jain SC. Design and synthesis of spiro[indole-thiazolidine]spiro[ indole-pyrans] as antimicrobial agents. Bioorg Med Chem Lett. 2011;21(18):5465-9. https://doi.org/10.1016/j.bmcl.2011.06.121

Jain P, Utreja D, Poonam S. An efficacious synthesis of N-1 C-3 substituted indole derivatives and their antimicrobial studies. Journal of Heterocyclic Chemistry. 2019; 57(1):428-35. https://doi.org/10.1002/jhet.3799

Kaur J, Utreja D, Ekta, Nisha J, Shivali S. Recent Developments in the Synthesis and Antimicrobial Activity of Indole and its Derivatives. Curr Org Synth. 2019;16(1):17-37. https://doi.org/10.2174/1570179415666181113144939

Brasil. Agência Nacional de Vigilância Sanitária (ANVISA). Gerência Geral de Tecnologia em Serviços de Saúde (GGTSS). Gerência de Vigilância e Monitoramento em Serviços de Saúde (GVMSS). Plano Nacional para a Prevenção e o Controle da Resistência Microbiana nos Serviços de Saúde; 2017 [cited 2017 Nov 03]. Available from: http://portal.anvisa.gov.br/documents/33852/271855/Plano+Nacional+para+a+Prevenção+e+o+Controle+da+Resistência+Microbiana+nos+Serviços+de+Saúde

Park SH, Kim JK and Park K. In vitro antimicrobial activities of fusidic acid and retapamulin against mupirocin – and methicillin-resistant Staphylococcus aureus. Ann. Dermatol. 2015; 27: 551-6. https://doi.org/10.5021/ad.2015.27.5.551

Downloads

Publicado

2021-12-20

Como Citar

Ferreira, L. B., Silva, E. E. da, Lentz, S. A. M., Azeredo, J. B. de, Braga, A. L., Machado, M. M., … Martins, A. F. (2021). Atividade Anti-Staphylococcus aureus Meticilina Resistente (MRSA) de um novo composto 3-Calcogenil Indol. Scientia Medica, 31(1), e41325. https://doi.org/10.15448/1980-6108.2021.1.41325

Edição

v. 31 n. 1 (2021): Volume Único

Seção

Artigo de Pesquisa

Licença

Copyright (c) 2021 Scientia Medica

Creative Commons License
Este trabalho está licenciado sob uma licença Creative Commons Attribution 4.0 International License.