Objective: This study aimed to evaluate the antifungal and antibiofilm of 2-bromo-N-phenylacetamide (A1Br) against Cryptococcus neoformans in vitro.

Methods: The compound was characterized by infrared and 1H-nuclear magnetic resonance spectrometry data. Minimum inhibitory concentration (MIC) was determined using the plate dilution method and biofilm formation inhibition of the crystal violet assay.

Results: A1Br inhibited the growth of C. neoformans with MIC of 0.25 and 0.5 μg/ml and has good antibiofilm activity MIC ×4, with ≥80% inhibition growth.

Conclusions: Thus, A1Br shows potential antifungal and antibiofilm agents for the treatment of infections caused by C. neoformans, as well as the eradication of cryptococcal colonization of medical prosthetic devices.

Keywords: Antifungal, Biofilm, 2-bromo-N-phenylcetamide, Cryptococcus neoformans, in vitro

Author Biography

ABRAHÃO ALVES DE OLIVEIRA-FILHO, Department of , Federal University of Campina Grande, Patos, Brazil.

3 Academic Unit of Biological Sciences, Health Center and Rural Technology, Federal University of Campina Grande, Patos, Paraíba, Brazil.


1. Herkert PF, Hagen F, Pinheiro RL, Muro MD, Meis JF, Queiroz- Telles F. Ecoepidemiology of Cryptococcus gattii in developing countries. J Fungi (Basel) 2017;3:62.
2. Maziarz EK, Perfect JR. Cryptococcosis. Infect Dis Clin North Am 2016;30:179-206.
3. Rajasingham R, Smith RM, Park BJ, Jarvis JN, Govender NP, Chiller TM, et al. Global burden of disease of HIV-associated cryptococcal meningitis: An updated analysis. Lancet Infect Dis 2017;17:873-81.
4. Negroni R. Cryptococcosis. Clin Dermatol 2012;30:599-609.
5. Sardi JC, Scorzoni L, Bernardi T, Fusco-Almeida AM, Giannini MJ. Candida species: Current epidemiology, pathogenicity, biofilm formation, natural antifungal products, and new therapeutic options. J Med Microbiol 2013;62:10-24.
6. Tumbarello M, Posteraro B, Trecarichi EM, Fiori B, Rossi M, Porta R, et al. Biofilm production by Candida species and inadequate antifungal therapy as predictors of mortality for patients with candidemia. J Clin Microbiol 2007;45:1843-50.
7. Pakshir K, Zomorodian K, Karamitalab M, Jafari M, Taraz H, Ebrahimi H. Phospholipase, esterase and hemolytic activities of Candida spp. Isolated from onychomycosis and oral lichen planus lesions. J Mycol Med 2013;23:113-8.
8. Silva NC, Nery JM, Dias AL. Aspartic proteinases of Candida spp.: Role in pathogenicity and antifungal resistance. Mycoses 2014;57:1-11.
9. Yin W, Wang Y, Liu L, He J. Biofilms: The microbial protective clothing in extreme environments. Int J Mol Sci 2019;20:3423.
10. Santos AL, De Mello TP, Ramos LS, Branquinha MH. Biofilm: A robust and efficient barrier to antifungal chemotherapy. Int J Antimicrob Agents 2015;1:e101.
11. de Mello TP, de Souza Ramos L, Braga-Silva LA, Branquinha MH, Dos Santos AL. Fungal biofilm-a real obstacle against an efficient therapy: Lessons from Candida. Curr Top Med Chem 2017;
12. Martinez LR, Casadevall A. Susceptibility of Cryptococcus neoformans biofilms to antifungal agents in vitro. Antimicrob Agents Chemother 2006;50:1021-33.
13. Aschale M. Synthesis and antimicrobial evaluation of some novel substituted 2-chloroacetanalides. Int J Chemtech Res 2012;4:1437-41.
14. Srikanth J, Sandeep T, Divya K, Govindarajan R. Screening of in vitro anti-inflammatory activity of some newly synthesized 1,3-thiazine derivatives. Int J Pharm Chem Res 2013;3:213-20.
15. Verma AK, Martin A, Singh AK. Synthesis, characterization and evaluation of anti-inflammatory and analgesic activity of benzothiazole derivatives. Indian J Pharm Biol Res 2014;2:84-9.
16. Pattan SR, Ali MS, Pattan JS, Purohit SS, Reddy VV, Nataraj BR. Synthesis and microbiological evaluation of 2-acetanilido-4- arylthiazole derivatives. Indian J Chem 2006;45:1929-32.
17. Konda RK, Nuthakki VK, Nagarjuna R. Synthesis, characterization and pharmacological screening of substituted sulphonamide derivatives. Sch Acad J Pharm 2014;3:344-9.
18. Álvarez G, Varela J, Cruces E, Fernández M, Gabay M, Leal SM, et al.Identification of a new amide-containing thiazole as a drug candidate for treatment of Chagas disease. Antimicrob Agents Chemother 2015;59:1398-404.
19. Brasil PF, de Freitas JA, Barreto AL, Adade CM, Reis de Sá LF, Constantino-Teles P, et al. Antiproliferative and ultrastructural effects of phenethylamine derivatives on promastigotes and amastigotes of Leishmania (Leishmania) Infantum chagasi. Parasitol Int 2017;66:47-55.
20. Xie JL, Polvi EJ, Shekhar-Guturja T, Cowen LE. Elucidating drug resistance in human fungal pathogens. Future Microbiol 2014;9:523-42.
21. Cleeland R, Squires E. Evaluation of new antimicrobials vitro and experimental animal infection. In: Lorian V, editor. Antibiotics in Laboratory Medicine. 3rd ed. Baltimore: Williams and Wilkiam; 1991. p. 739-87.
22. Hadacek F, Greger H. Testing of antifungal natural products: Methodologies, comparability of results and assay choice. Phytochem Anal 2000;11:137-47.
23. Clinical and Laboratory Standards Institute. Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeasts. 3rd ed. London, United Kingdom: Clinical and Laboratory Standards Institute; 2008.
24. Sartoratto A, Machado AL, Delarmelina C, Figueira GM, Duarte MC, Rehder VL. Composition and antimicrobial activity of essential oils from aromatic plants used in Brazil. Braz J Microbiol 2004;35:275-80.
25. Balasubramanian D, Schneper L, Merighi M, Smith R, Narasimhan G, Lory S, et al. The regulatory repertoire of Pseudomonas aeruginosa AmpC ß-lactamase regulator AmpR includes virulence genes. PLoS One 2012;7:e34067.
26. Katke SA, Amrutkar SV, Bhor RJ, Khairnar MV. Synthesis of biologically active 2-chloro-n-alkyl/aryl acetamide derivatives. Int J Pharm Sci Res 2011;2:148-56.
27. Machado GD, de Andrade SF, Pippi B, Bergamo VZ, Berlitz SJ, Lopes W, et al. Chloroacetamide derivatives as a promising topical treatment for fungal skin infections. Mycologia. 2019;111:612-23.
28. Taff HT, Mitchell KF, Edward JA, Andes DR. Mechanisms of Candida biofilm drug resistance. Future Microbiol 2013;8:1325-37.
29. El-Azizi M, Farag N, Khardori N. Antifungal activity of amphotericin B and voriconazole against the biofilms and biofilm-dispersed cells of Candida albicans employing a newly developed in vitro pharmacokinetic model. Ann Clin Microbiol Antimicrob 2015;14:21.
30. Kwasny SM, Opperman TJ. Static biofilm cultures of gram-positive pathogens grown in a microtiter format used for anti-biofilm drug discovery. Curr Protoc Pharmacol 2010;
31. Martinez LR, Casadevall A. Biofilm formation by Cryptococcus neoformans. Microbiol Spectr 2015;3
30 Views | 51 Downloads
How to Cite
DE MELO, T. R., L. V. CORDEIRO, H. D. DA SILVA SOUZA, P. F. DE ATHAYDE-FILHO, A. A. DE OLIVEIRA-FILHO, S. B. FERREIRA, and E. D. OLIVERIA LIMA. “ANTIFUNGAL AND ANTIBIOFILM ACTIVITY OF 2-BROMO-N-PHENYLCETAMIDE AGAINST CRYPTOCOCCUS NEOFORMANS”. Asian Journal of Pharmaceutical and Clinical Research, Vol. 13, no. 12, Dec. 2020, pp. 173-6, doi:10.22159/ajpcr.2020.v13i12.39834.
Original Article(s)