Publicado

2022-02-04

In silico and in vitro analysis of a new potential antifungal substance, 2-Bromo-Nphenylacetamide, against invasive candidiasis isolates

Análisis in silico e in vitro de una nueva sustancia antifúngica potencial, 2-Bromo-N-fenilacetamida, contra cepas de candidiasis invasive

Análise in silico e in vitro de uma nova substância antifúngica potencial, 2-Bromo-N-fenilacetamida, contra isolados de candidíase invasiva

DOI:

https://doi.org/10.15446/rcciquifa.v50n3.100227

Palabras clave:

Candida albicans, Candida parapsilosis, 2-Bromo-N-phenylacetamide, antifungal (en)
Candida albicans, Candida parapsilosis, 2-bromo-N-fenilacetamida, antifúngico (es)
Candida albicans, Candida parapsilosis, 2-bromo-N-fenilacetamida, Antifúngico (pt)

Descargas

Autores/as

  • Romulo Pereira de Moura Sousa Federal University of Paraíba, Laboratory of Mycology, Department of Pharmaceutical Science, Health Sciences Center, João Pessoa
  • Daniele de Figuerêdo Silva Federal University of Paraíba, Laboratory of Mycology, Department of Pharmaceutical Science, Health Sciences Center, João Pessoa
  • Neuza Maria Cavalcante Oliveira Federal University of Paraíba, Laboratory of Mycology, Department of Pharmaceutical Science, Health Sciences Center, João Pessoa
  • Zélia Braz Vieira Da Silva Pontes Federal University of Paraíba, Laboratory of Mycology, Department of Pharmaceutical Science, Health Sciences Center, João Pessoa
  • Hermes Diniz Neto Federal University of Paraíba, Laboratory of Mycology, Department of Pharmaceutical Science, Health Sciences Center, João Pessoa
  • Laísa Vilar Cordeiro Federal University of Paraíba, Laboratory of Mycology, Department of Pharmaceutical Science, Health Sciences Center, João Pessoa
  • Pedro Thiago Ramalho de Figueiredo Federal University of Paraíba, Laboratory of Mycology, Department of Pharmaceutical Science, Health Sciences Center, João Pessoa
  • Rafael Farias de Oliveira Federal University of Paraíba, Laboratory of Mycology, Department of Pharmaceutical Science, Health Sciences Center, João Pessoa
  • Helivaldo Diógenes da Silva Souza Federal University of Paraíba, Laboratory of Mycology, Department of Pharmaceutical Science, Health Sciences Center, João Pessoa
  • Petrônio Filgueiras de Athayde Filho Federal University of Paraíba, Laboratory of Mycology, Department of Pharmaceutical Science, Health Sciences Center, João Pessoa
  • Edeltrudes de Oliveira Lima Federal University of Paraíba, Laboratory of Mycology, Department of Pharmaceutical Science, Health Sciences Center, João Pessoa

Introduction: invasive candidiasis is related to high rates of morbidity and mortality. There are few classes of drugs available for the treatment of this type of infection and the index of resistant strains is increasing. Such circumstances highlight that the search for new pharmacotherapeutic alternatives is increasingly necessary. This study investigated 2-Bromo-N-phenylacetamide, a substance whose antifungal activity has not yet been reported. Objective: to evaluate its activity against invasive candidiasis isolates, by determining the minimum inhibitory and fungicide concentrations. Meth-odology: molecular docking was performed to investigate the possible mechanism of action of the substance. The substance was also associated with fluconazole, to assess the viability of the combination in clinical practice. The minimum inhibitory concen-trations ranged between 4 to 32 μg/mL, and it acts in a fungicidal way. Results: molec-ular docking suggests that 2-Bromo-N-phenylacetamide possibly acts on the fungal plasma membrane. And the association of 2-Bromo-N-phenylacetamide with flucon-azole against resistant strains showed an indifferent effect. Conclusion: further studies should be carried out to elucidate the potential of this substance, which may become a future drug candidate to treat invasive candidiasis and other fungal infections.

Introducción: la candidiasis invasiva está relacionada con altas tasas de morbilidad y mortalidad. Hay pocas clases de medicamentos disponibles para el tratamiento de este tipo de infección y el índice de cepas resistentes está aumentando. Tales circunstancias ponen de relieve que la búsqueda de nuevas alternativas farmacoterapéuticas es cada vez más necesaria. Este estudio investigó la 2-Bromo-N-fenilacetamida, una sustancia cuya actividad antifúngica aún no se ha informado. Objetivo: evaluar su actividad frente a aislados de candidiasis invasiva, mediante la determinación de las concentra-ciones mínimas inhibitorias y fungicidas. Metodología: se realizó un acoplamiento molecular para investigar el posible mecanismo de acción de la sustancia. La sustancia también se asoció con fluconazol, para evaluar la viabilidad de la combinación en la práctica clínica. Las concentraciones mínimas inhibidoras oscilaron entre 4 a 32 μg/mL y actúa de forma fungicida. Resultados: el acoplamiento molecular sugiere que la 2-Bromo-N-fenilacetamida posiblemente actúa sobre la membrana plasmática de los hongos. Y la asociación de 2-Bromo-N-fenilacetamida con fluconazol contra cepas resistentes mostró un efecto indiferente. Conclusión: deben realizarse más estudios para dilucidar el potencial de esta sustancia, que puede convertirse en un futuro candi-dato a fármaco para tratar la candidiasis invasiva y otras infecciones fúngicas.

Introducão:a candidíase invasiva está relacionada a altas taxas de morbidade e morta-lidade. Existem poucas classes de medicamentos disponíveis para o tratamento desse tipo de infecção e o índice de cepas resistentes está aumentando. Tais circunstâncias evidenciam que a busca por novas alternativas farmacoterapêuticas é cada vez mais necessária. Este estudo investigou a 2-Bromo-N-fenilacetamida, uma substância cuja atividade antifúngica ainda não foi relatada. Objetivo: avaliar sua atividade contra isolados de candidíase invasiva, por meio da determinação das concentrações mínimas inibitórias e fungicidas. Metodologia: o docking molecular foi realizado para inve-stigar o possível mecanismo de ação da substância. A substância também foi associada ao fluconazol, para avaliar a viabilidade da associação na prática clínica. As concen-trações inibitórias mínimas variaram entre 4 a 32 μg/Ml e atuam de forma fungicida. Resultados: o docking molecular sugere que a 2-Bromo-N-fenilacetamida possivel-mente atua na membrana plasmática do fungo. E a associação de 2-Bromo-N-fenilace-tamida com fluconazol contra cepas resistentes mostrou efeito indiferente. Conclusão: Novos estudos devem ser realizados para elucidar o potencial dessa substância, que pode se tornar uma futura droga candidata ao tratamento de candidíase invasiva e outras infecções fúngicas.

Referencias

A.M. Doi, A.C.C. Pignatari, M.B. Edmond, A.R. Marra, L.F.A. Camargo, R.A. Siqueira, V.P. Mota, A.L. Colombo, Epidemiolog y and microbiologic characte-rization of nosocomial candidemia from a Brazilian national surveillance pro-gram,PloS One, 11(1), e0146909 (2016). DOI: https://doi.org/10.1371/journal.pone.0146909

M.F. Gonzalez-Lara, L. Ostrosky-Zeichner, Invasive candidiasis, Seminars in Respiratory and Critical Care Medicine3. 4. , 41(01), 3-12 (2020). DOI: https://doi.org/10.1055/s-0040-1701215

M.C. Arendrup, T.F. Patterson, Multidrug-resistant Candida: epidemio-log y, molecular mechanisms, and treatment,The Journal of Infectious Diseases, 216(Suppl. 3), S445-S451 (2017). DOI: https://doi.org/10.1093/infdis/jix131

A. Moraes-Nicola, P. Albuquerque, H. Costa-Paes, L. Fernandes, F.F. Costa, E. Seli-Kioshima, A.K. Rodrigues-Abadio, A. Lorenzetti-Bocca, M. Sueli-Felipe, Antifungal drugs: new insights in research & development, Pharmacolog y & Therapeutics,195, 21-38 (2019). DOI: https://doi.org/10.1016/j.pharmthera.2018.10.008

C.P. Kaushik, R. Luxm, M. Kumar, D. Singh, K. Krishan, A. Pahwa, One-pot facile synthesis, crystal structure and antifungal activity of 1,2,3-triazoles bridged with amine-amide functionalities, Synthetic Communications, 49(1), 118-128 (2019). DOI: https://doi.org/10.1080/00397911.2018.1544371

H. Xie, D. Ng, S.N. Savinov, B. Dey, P.D. Kwong, R. Wyatt, A.B. Smith, W.A. Hendrickson, Structure-activity relationships in the binding of chemically deri-vatized CD4 to gp120 from human immunodeficiency virus, Journal of Medici-nal Chemistry, 50(20), 4898-4908 (2007). DOI: https://doi.org/10.1021/jm070564e

L. Cleeland, E. Squires, Evaluation of new antimicrobials in vitro and experimen-tal animal infections, in: V. Lorian (editor), Antibiotics in laboratory medicine, Williams & Wilkins, Baltimore (MD), 1991, p. 739-788.

F. Hadacek, H. Greger, Testing of antifungal natural products: methodologies, comparability of results and assay choice, Phytochemical Analysis, 11(3), 137-147 (2000). DOI: https://doi.org/10.1002/(SICI)1099-1565(200005/06)11:3<137::AID-PCA514>3.0.CO;2-I

National Committee for Clinical Laboratory Standards, Reference method for broth dilution antifungal susceptibility testing of yeasts: Approved standard, 2ndedition, NCCLS, Wayne, 2008, 29 p.

L. Sousa-Pinheiro, A.A. de Oliveira Filho, F. Queiroga-Sarmento-Guerra, C. Pinheiro de Menezes, S. Golzio dos Santos, J. Pereira de Sousa, T. Barbosa-Dantas, E. De Oliveira-Lima, Antifungal activity of the essential oil isolated from Laurus nobilis L. against Cryptococcus neoformans strains,Journal of Applied Pharmaceutical Sciences, 7(5), 115-118 (2017).

R. Thomsen, M.H. Christensen, MolDock: A new technique for High-Accuracy Molecular Docking, Journal of Medicinal Chemistry, 49(11), 3315-3321 (2006). DOI: https://doi.org/10.1021/jm051197e

RCSB PDB, https://www.rcsb.org, accessed in March 2020.

X. Wu, Z. Li, X. Li, Y. Tian, Y. Fan, C. Yu, B. Zhou, Y. Liu, R. Xiang, L. Yang, Synergistic effects of antimicrobial peptide DP7 combined with antibiotics aga-inst multidrug-resistant bacteria, Drug Design, Development and Therapy, 11, 939-946 (2017). DOI: https://doi.org/10.2147/DDDT.S107195

D. Hall, R. Bonifas, L. Stapert, M. Thwaites, D.L. Shinabarger, C.M. Pillar, In vitro potency and fungicidal activity of CD101, a novel echinocandin, against recent clinical isolates of Candida spp., Diagnostic Microbiolog y and Infectious Disease, 89(3), 205-211 (2017). DOI: https://doi.org/10.1016/j.diagmicrobio.2017.07.007

T.Y. Hargrove, L. Friggeri, Z. Wawrzak, A. Qi, W.J. Hoekstra, R.J. Schotzinger, J.D. York, P. Guengerich, G.I. Lepesheva,Structural analyses of Candida albicanssterol 14α-demethylase complexed with azole drugs address the molecular basis of azole-mediated inhibition of fungal sterol biosynthesis,Journal of Biological Chemistry, 292(16), 6728-6743 (2017). DOI: https://doi.org/10.1074/jbc.M117.778308

S.M. Cutfield, G.J. Davies, G. Murshudov, B.F. Anderson, P.C.E. Moody, P.A. Sullivan, J.F. Cutfield, The structure of the exo-β-(1,3)-glucanase from Candida albicans in native and bound forms: relationship between a pocket and groove in family 5 glycosyl hydrolases,Journal of Molecular Biolog y, 294(3), 771-783 (1999). DOI: https://doi.org/10.1006/jmbi.1999.3287

R.E. Lewis, D.J. Diekema, S.A. Messer, M.A. Pfaller, M.E. Klepser, Comparison of Etest, chequerboard dilution and time–kill studies for the detection of synerg y or antagonism between antifungal agents tested against Candida species, Journal of Antimicrobial Chemotherapy, 49(2), 345-351 (2002). DOI: https://doi.org/10.1093/jac/49.2.345

J. Correa-Royero, V. Tangarife, C. Durán, E. Stashenko, A. Mesa-Arango, In vitroantifungal activity and cytotoxic effect of essential oils and extracts of medicinal and aromatic plants against Candida krusei and Aspergillus fumigatus, Revista Brasileira de Farmacognosia, 20(5), 734-741 (2010). DOI: https://doi.org/10.1590/S0102-695X2010005000021

Cómo citar

APA

de Moura Sousa, R. P., de Figuerêdo Silva, D., Cavalcante Oliveira, N. M., Vieira Da Silva Pontes, Z. B., Diniz Neto, H., Vilar Cordeiro, L., Ramalho de Figueiredo, P. T., Farias de Oliveira, R., da Silva Souza, H. D., de Athayde Filho, P. F. y de Oliveira Lima, E. (2022). In silico and in vitro analysis of a new potential antifungal substance, 2-Bromo-Nphenylacetamide, against invasive candidiasis isolates. Revista Colombiana de Ciencias Químico-Farmacéuticas, 50(3). https://doi.org/10.15446/rcciquifa.v50n3.100227

ACM

[1]
de Moura Sousa, R.P., de Figuerêdo Silva, D., Cavalcante Oliveira, N.M., Vieira Da Silva Pontes, Z.B., Diniz Neto, H., Vilar Cordeiro, L., Ramalho de Figueiredo, P.T., Farias de Oliveira, R., da Silva Souza, H.D., de Athayde Filho, P.F. y de Oliveira Lima, E. 2022. In silico and in vitro analysis of a new potential antifungal substance, 2-Bromo-Nphenylacetamide, against invasive candidiasis isolates. Revista Colombiana de Ciencias Químico-Farmacéuticas. 50, 3 (feb. 2022). DOI:https://doi.org/10.15446/rcciquifa.v50n3.100227.

ACS

(1)
de Moura Sousa, R. P.; de Figuerêdo Silva, D.; Cavalcante Oliveira, N. M.; Vieira Da Silva Pontes, Z. B.; Diniz Neto, H.; Vilar Cordeiro, L.; Ramalho de Figueiredo, P. T.; Farias de Oliveira, R.; da Silva Souza, H. D.; de Athayde Filho, P. F.; de Oliveira Lima, E. In silico and in vitro analysis of a new potential antifungal substance, 2-Bromo-Nphenylacetamide, against invasive candidiasis isolates. Rev. Colomb. Cienc. Quím. Farm. 2022, 50.

ABNT

DE MOURA SOUSA, R. P.; DE FIGUERÊDO SILVA, D.; CAVALCANTE OLIVEIRA, N. M.; VIEIRA DA SILVA PONTES, Z. B.; DINIZ NETO, H.; VILAR CORDEIRO, L.; RAMALHO DE FIGUEIREDO, P. T.; FARIAS DE OLIVEIRA, R.; DA SILVA SOUZA, H. D.; DE ATHAYDE FILHO, P. F.; DE OLIVEIRA LIMA, E. In silico and in vitro analysis of a new potential antifungal substance, 2-Bromo-Nphenylacetamide, against invasive candidiasis isolates. Revista Colombiana de Ciencias Químico-Farmacéuticas, [S. l.], v. 50, n. 3, 2022. DOI: 10.15446/rcciquifa.v50n3.100227. Disponível em: https://revistas.unal.edu.co/index.php/rccquifa/article/view/100227. Acesso em: 26 abr. 2025.

Chicago

de Moura Sousa, Romulo Pereira, Daniele de Figuerêdo Silva, Neuza Maria Cavalcante Oliveira, Zélia Braz Vieira Da Silva Pontes, Hermes Diniz Neto, Laísa Vilar Cordeiro, Pedro Thiago Ramalho de Figueiredo, Rafael Farias de Oliveira, Helivaldo Diógenes da Silva Souza, Petrônio Filgueiras de Athayde Filho, y Edeltrudes de Oliveira Lima. 2022. «In silico and in vitro analysis of a new potential antifungal substance, 2-Bromo-Nphenylacetamide, against invasive candidiasis isolates». Revista Colombiana De Ciencias Químico-Farmacéuticas 50 (3). https://doi.org/10.15446/rcciquifa.v50n3.100227.

Harvard

de Moura Sousa, R. P., de Figuerêdo Silva, D., Cavalcante Oliveira, N. M., Vieira Da Silva Pontes, Z. B., Diniz Neto, H., Vilar Cordeiro, L., Ramalho de Figueiredo, P. T., Farias de Oliveira, R., da Silva Souza, H. D., de Athayde Filho, P. F. y de Oliveira Lima, E. (2022) «In silico and in vitro analysis of a new potential antifungal substance, 2-Bromo-Nphenylacetamide, against invasive candidiasis isolates», Revista Colombiana de Ciencias Químico-Farmacéuticas, 50(3). doi: 10.15446/rcciquifa.v50n3.100227.

IEEE

[1]
R. P. de Moura Sousa, «In silico and in vitro analysis of a new potential antifungal substance, 2-Bromo-Nphenylacetamide, against invasive candidiasis isolates», Rev. Colomb. Cienc. Quím. Farm., vol. 50, n.º 3, feb. 2022.

MLA

de Moura Sousa, R. P., D. de Figuerêdo Silva, N. M. Cavalcante Oliveira, Z. B. Vieira Da Silva Pontes, H. Diniz Neto, L. Vilar Cordeiro, P. T. Ramalho de Figueiredo, R. Farias de Oliveira, H. D. da Silva Souza, P. F. de Athayde Filho, y E. de Oliveira Lima. «In silico and in vitro analysis of a new potential antifungal substance, 2-Bromo-Nphenylacetamide, against invasive candidiasis isolates». Revista Colombiana de Ciencias Químico-Farmacéuticas, vol. 50, n.º 3, febrero de 2022, doi:10.15446/rcciquifa.v50n3.100227.

Turabian

de Moura Sousa, Romulo Pereira, Daniele de Figuerêdo Silva, Neuza Maria Cavalcante Oliveira, Zélia Braz Vieira Da Silva Pontes, Hermes Diniz Neto, Laísa Vilar Cordeiro, Pedro Thiago Ramalho de Figueiredo, Rafael Farias de Oliveira, Helivaldo Diógenes da Silva Souza, Petrônio Filgueiras de Athayde Filho, y Edeltrudes de Oliveira Lima. «In silico and in vitro analysis of a new potential antifungal substance, 2-Bromo-Nphenylacetamide, against invasive candidiasis isolates». Revista Colombiana de Ciencias Químico-Farmacéuticas 50, no. 3 (febrero 4, 2022). Accedido abril 26, 2025. https://revistas.unal.edu.co/index.php/rccquifa/article/view/100227.

Vancouver

1.
de Moura Sousa RP, de Figuerêdo Silva D, Cavalcante Oliveira NM, Vieira Da Silva Pontes ZB, Diniz Neto H, Vilar Cordeiro L, Ramalho de Figueiredo PT, Farias de Oliveira R, da Silva Souza HD, de Athayde Filho PF, de Oliveira Lima E. In silico and in vitro analysis of a new potential antifungal substance, 2-Bromo-Nphenylacetamide, against invasive candidiasis isolates. Rev. Colomb. Cienc. Quím. Farm. [Internet]. 4 de febrero de 2022 [citado 26 de abril de 2025];50(3). Disponible en: https://revistas.unal.edu.co/index.php/rccquifa/article/view/100227

Descargar cita

CrossRef Cited-by

CrossRef citations0

Dimensions

PlumX

Visitas a la página del resumen del artículo

294

Descargas

Los datos de descargas todavía no están disponibles.

Licencia

Creative Commons License

Esta obra está bajo una licencia internacional Creative Commons Atribución 4.0.

El Departamento de Farmacia de la Facultad de Ciencias de la Universidad Nacional de Colombia  autoriza la fotocopia de artículos y textos para fines de uso académico o interno de las instituciones citando la fuente. Las ideas emitidas por los autores son responsabilidad expresa de estos y no de la revista.

Todo el contenido de esta revista, excepto dónde está identificado, está bajo una Licencia Creative Commons de Atribución 4.0 aprobada en Colombia. Consulte la normativa en: http://co.creativecommons.org/?page_id=13