دورية أكاديمية
Antifungal activity of 2-chloro-N-phenylacetamide, docking and molecular dynamics studies against clinical isolates of Candida tropicalis and Candida parapsilosis.
| العنوان: | Antifungal activity of 2-chloro-N-phenylacetamide, docking and molecular dynamics studies against clinical isolates of Candida tropicalis and Candida parapsilosis. |
|---|---|
| المؤلفون: | Silva SL; Postgraduate Program in Natural and Bioactive Synthetic Products, Department of Pharmaceutical Sciences, Federal University of Paraiba, João Pessoa, Paraíba, Brazil., de Oliveira Pereira F; Biochemistry Laboratory, Academic Unit of Health, Education and Health Center, Federal University of Campina Grande, Cuité, Paraíba, Brazil., Cordeiro LV; Postgraduate Program in Natural and Bioactive Synthetic Products, Department of Pharmaceutical Sciences, Federal University of Paraiba, João Pessoa, Paraíba, Brazil., Neto HD; Postgraduate Program in Natural and Bioactive Synthetic Products, Department of Pharmaceutical Sciences, Federal University of Paraiba, João Pessoa, Paraíba, Brazil., Dos Santos Maia M; Postgraduate Program in Natural and Bioactive Synthetic Products, Department of Pharmaceutical Sciences, Federal University of Paraiba, João Pessoa, Paraíba, Brazil., da Silva Souza HD; Bioenergy and Organic Synthesis Research Laboratory, Department of Chemistry, University of Paraiba, João Pessoa, Paraíba, Brazil., de Athayde-Filho PF; Bioenergy and Organic Synthesis Research Laboratory, Department of Chemistry, University of Paraiba, João Pessoa, Paraíba, Brazil., Scotti MT; Postgraduate Program in Natural and Bioactive Synthetic Products, Department of Pharmaceutical Sciences, Federal University of Paraiba, João Pessoa, Paraíba, Brazil., Scotti L; Postgraduate Program in Natural and Bioactive Synthetic Products, Department of Pharmaceutical Sciences, Federal University of Paraiba, João Pessoa, Paraíba, Brazil., de Oliveira Lima E; Postgraduate Program in Natural and Bioactive Synthetic Products, Department of Pharmaceutical Sciences, Federal University of Paraiba, João Pessoa, Paraíba, Brazil. |
| المصدر: | Journal of applied microbiology [J Appl Microbiol] 2022 May; Vol. 132 (5), pp. 3601-3617. Date of Electronic Publication: 2022 Mar 15. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Oxford University Press Country of Publication: England NLM ID: 9706280 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1365-2672 (Electronic) Linking ISSN: 13645072 NLM ISO Abbreviation: J Appl Microbiol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2022- : Oxford : Oxford University Press Original Publication: Oxford : Published for the Society for Applied Bacteriology by Blackwell Science, c1997- |
| مواضيع طبية MeSH: | Antifungal Agents*/pharmacology , Antifungal Agents*/therapeutic use , Candida tropicalis*, Biofilms ; Candida parapsilosis ; Drug Resistance, Fungal ; Fluconazole/pharmacology ; Humans ; Microbial Sensitivity Tests ; Molecular Docking Simulation ; Molecular Dynamics Simulation |
| مستخلص: | Aims: This study evaluated the antifungal, antibiofilm and molecular docking of 2-chloro-N-phenylacetamide against clinical isolates of Candida tropicalis and Candida parapsilosis. Methods and Results: Minimum inhibitory concentration (MIC) of the test drugs was determined by microdilution. A1Cl obtained MIC values ranging from 16 and 256 μg/ml. Fluconazole MIC ranging from 16 and 512 μg/ml. MIC of A1Cl showed fungicide activity, emphasizing the solid antifungal potential of this drug. An association study was performed with A1Cl and fluconazole (checkerboard), revealing indifference by decreasing. Thus, we conducted this study using A1Cl isolated. In the micromorphological assay, the test drugs reduced the production of virulence structures compared to the control (concentration-dependent effect). A1Cl inhibited in vitro biofilm formation at all concentrations tested (1/4MIC to 8 × MIC) (p < 0.05) and reduced mature biofilm biomass (p < 0.05) against C. tropicalis and C. parapsilosis. In the ex vivo biofilm susceptibility testing (human nails fragments), A1Cl inhibited biofilm formation and reduced mature biofilm biomass (p < 0.05) more than 50% at MIC. Fluconazole had a similar effect at 4 × MIC. In silico studies suggest that the mechanism of antifungal activity of A1Cl involves the inhibition of the enzyme dihydrofolate reductase (DHFR) rather than geranylgeranyltransferase-I. Conclusions: The results suggest that A1Cl is a promising antifungal agent. Furthermore, this activity is related to attenuation of expression of virulence factors and antibiofilm effects against C. tropicalis and C. parapsilosis. Significance and Impact of the Study: Our study provides the first evidence that A1Cl, a novel synthetic drug, has fungicidal effects against C. tropicalis and C. parapsilosis. Furthermore, in vitro and ex vivo biofilms assays have demonstrated the potential antibiofilm of A1Cl. The mechanism of action involves inhibiting the enzyme DHFR, which was supported by in silico analyses. Therefore, this potential can be explored as a therapeutic alternative for onychomycosis and, at the same time, contribute to decreasing the resistance of clinical isolates of C. tropicalis and C. parapsilosis. (© 2022 Society for Applied Microbiology.) |
| References: | Alves D. N., Monteiro, A. F. M., Andrade, P. N., Lazarini, J. G., Abílio, G. M. F., Guerra, F. Q. S., Scotti, M. T., Scotti, L., Rosalen, P. L. And Castro, R. D. D. (2020) Docking prediction, antifungal activity, anti-biofilm effects on Candida spp., and toxicity against human cells of cinnamaldehyde. Molecules 25(24), 5969. Alves, L.A., Freires, I.D.A., Pereira, T.M., Souza, A.D., Lima, E.D.O. & Castro, R.D. (2013) Effect of Schinus terebinthifolius on Candida albicans growth kinetics, cell wall formation and micromorphology. Acta Odontologica Scandinavica, 71(3-4), 965-971. Andrés, T.S. & Alexandro, B. (2020) Candida onychomycosis: an old problem in modern times. Current Fungal Infection Reports, 14(3), 206-216. Arrua, J.M.M., Rodrigues, L.A.S., Pereira, F.O. & Lima, E.O. (2015) Prevalence of Candida tropicalis and Candida krusei in onychomycosis in João Pessoa, Paraiba, Brazil from 1999 to 2010. Proceedings of the Brazilian Academy of Sciences, 87(3), 1819-1822. Balasubramanian, D., Schneper, L., Merighi, M., Smith, R., Narasimhan, G., Lory, S. et al. (2012) The regulatory repert oire of Pseudomonas aeruginosa AmpC ß-lactamase regulator AmpR includes virulence genes. PLoS ONE, 7(3), 34067. Barros, P.P., Rossoni, R.D., De Souza, C.M., Scorzoni, L., Fenley, J.D.C. & Junqueira, J.C. (2020) Candida biofilms: an update on developmental mechanisms and therapeutic challenges. Mycopathologia, 185(3), 415-424. Bernstein, F.C., Koetzle, T.F., Williams, G.J., Meyer, E.F., Jr., Brice, M.D., Rodgers, J.R. et al. (1977) The Protein Data Bank: a computer-based archival file for macromolecular structures. Journal of Molecular Biology, 112(3), 535-542. Blakemore, D.C., Castro, L., Churcher, I., Rees, D.C., Thomas, A.W., Wilson, D.M. et al. (2018) Organic synthesis provides opportunities to transform drug discovery. Nature Chemistry, 10(4), 383-394. Bravo, H.R., Weiss-López, B., Lamborot, M. & Copaja, S. (2003) Chemical basis for theantimicrobialactivityofacetanilides. Journal of the Chilean Chemical Society, 48, 27-30. Cavalheiro, M. & Teixeira, M. C. (2018) Candida biofilms: threats, challenges, and promising strategies. Frontiers in Medicine 5, 28. Clinical and Laboratory Standards Institute. (2017) Reference method for broth dilution antifungal susceptibility testing of yeasts. Approved standard, 4th edition. CLSI document M27-A4. Wayne, PA: Clinical and Laboratory Standards Institute. Cordeiro, L.V., Neto, H.D., Figueiredo, P., Souza, H., Sousa, A., Andrade-Júnior, F. et al. (2020) Potential of 2-chloro-N-(4-fluoro-3-nitrophenyl) acetamide against Klebsiella pneumoniae and in vitro toxicity analysis. Molecules, 25(17), 3959. El-Houssaini, H.H., Elnabawy, O.M., Nasser, H.A. & Elkhatib, W.F. (2019) Influence of subinhibitory antifungal concentrations on extracellular hydrolases and biofilm production by Candida albicans recovered from Egyptian patients. BMC Infectious Diseases, 19(1), 1-9. Ferreira, E.S., Cordeiro, L.V., Silva, D.F., Souza, H.D.S., Athayde-Filho, P.F., Barbosa-Filho, J.M. et al. (2021) Antifungal activity and mechanism of action of 2-chloro-N-phenylacetamide: a new molecule with activity against strains of Aspergillus flavus. Anais da Academia Brasileira de Ciências, 93(3), 1-15. Gago, S., García-Rodas, R., Cuesta, I., Mellado, E. & Alastruey-Izquierdo, A. (2014) Candida parapsilosis, Candida orthopsilosis and Candida metapsilosis virulence in the non-conventional host Galleria mellonella. Virulence, 5(2), 278-285. Gupta, A.K., Jessie, C. & Neil, H.S. (2018) Antibiofilm treatment for onychomycosis and chronic fungal infections. Skin Appendage Disorders, 4(3), 136-140. Gupta, A.K., Mays, R.R., Versteeg, S.G., Shear, N.H. & Piguet, V. (2018) Update on current approaches to diagnosis and treatment of onychomycosis. Expert Review of Anti-Infective Therapy, 16(12), 929-938. Gupta, A.K., Stec, N., Summerbell, R.C., Shear, N.H., Piguet, V., Tosti, A. et al. (2020) Onychomycosis: a review. Journal of the European Academy of Dermatology and Venereology, 34(9), 1972-1990. Gupta, A.K., Versteeg, S.G., Shear, N.H., Piguet, V., Tosti, A. & Piraccini, B.M. (2019) A practical guide to curing onychomycosis: how to maximize cure at the patient, organism, treatment, and environmental level. American Journal of Clinical Dermatology, 20(1), 123-133. Joshi, T., Pundir, H. & Chandra, S. (2021) Deep-learning based repurposing of FDA-approved drugs against Candida albicans dihydrofolate reductase and molecular dynamics study. Journal of Biomolecular Structure & Dynamics, 1-17. https://doi.org/10.1080/07391102.2021.1911851. Khazir, J., Mir, B.A., Chashoo, G., Maqbool, T., Riley, D. & Pilcher, L. (2020) Design, synthesis, and anticancer evaluation of acetamide and hydrazine analogues of pyrimidine. Journal of Heterocyclic Chemistry, 57(3), 1306-1318. Kukhar, Y., Smagulova, A., Daniyarova, A., Baiduissenova, A. & Kiyan, V. (2020) Candida parapsilosis as a causative agent of onychomycosis in patient with cirrhosis of the liver. Journal of Fungi, 6(313), 1-6. Kwasny, S.M. & Opperman, T.J. (2010) Static biofilm cultures of Gram-positive pathogens grown in a microtiter format used for anti-biofilm drug discovery. Current Protocols in Pharmacology, 50(1), 13A-18A. Lewis, R.E., Diekema, D.J., Messer, S.A., Pfaller, M.A. & Klepser, M.E. (2002) Comparison of E-test, chequerboard dilution and time-kill studies for the detection of synergy or antagonism between antifungal agents tested against Candida species. The Journal of Antimicrobial Chemotherapy, 49, 345-351. Lipner, S.R., & Scher, R.K. (2019) Onychomycosis: clinical overview and diagnosis. Journal of the American Academy of Dermatology, 80(4), 835-851. Liu, G., Liu, F., Huang, H.Y., Shi, S., Zhang, Y.C., Yin, Z.Y. et al. (2019) Synthesis and antifungal activities of biquinazolinediselenides compounds. Afinidad, 76(586), 151-157. Lohse, M.B., Gulati, M., Craik, C.S., Johnson, A.D. & Nobile, C.J. (2020) Combination of antifungal drugs and protease inhibitors prevent Candida albicans biofilm formation and disrupt mature biofilms. Frontiers in Microbiology, 11, 1027. Marc, W., Andrew, J.H., David, S., Karl, D.H., Lee, F.K., David, P.B. et al. (1997) X-ray crystallographic studies of Candida albicans dihydrofolate reductase. International Journal of Biological Chemistry, 272(48), 30289-30298. Melo, T.R., Cordeiro, L.V., Souza, H.D.D.S., De Athayde-Filho, P.F., De Oliveira-Filho, A.A., Ferreira, S.B. et al. (2020) Antifungal and antibiofilm activity of 2-bromo-N-phenylcetamide against Cryptococcus neoformans. Asian Journal of Pharmaceutical and Clinical Research, 13(12), 173-176. Nett, J.E. & Andes, D.R. (2020) Contributions of the biofilm matrix to Candida pathogenesis. Journal of Fungi, 6(1), 1-9. Onsare, J.G. & Arora, D.S. (2014) Antibiofilm potential of flavonoids extracted from Moringa oleifera seed coat against Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans. Journal of Applied Microbiology, 118, 313-325. Paškevičius, A., Švedienė, J., Kiverytė, S., Bridžiuvienė, D., Vaitonis, G. & Jablonskienė, V. (2020) Candida distribution in onychomycosis and in vitro susceptibility to antifungal agents. Acta Dermatovenerologica Croatica, 28(4), 204-209. Pinzi, L. & Rastelli, G. (2019) Molecular docking: shifting paradigms in drug discovery. International Journal of Molecular Sciences, 20(18), 4331. Rajasekharan, S.K., Ramesh, S., Satish, A.S. & Lee, J. (2017) Antibiofilm and anti-β- lactamase activities of burdock root extract and chlorogenic acid against Klebsiella pneumoniae. Journal of Microbiology and Biotechnology, 27(3), 542-551. Sanad, S.M., Mekky, A.E. & El-Idreesy, T.T. (2021) Potential bacterial biofilm, MRSA, and inhibitors based on new morpholine-linked chromene-thiazole hybrids: one-post synthesis and in silico study. Journal of Molecular Structure, 1248, 131476. Shinde, R.R., Gaikwad, D. & Farooqui, M. (2020) Synthesis and antimicrobial activity of 2-(4-(benzo [d] thiazol-5-ylsulfonyl) piperazine-1-yl)-N-substituted acetamide derivatives. Journal of Heterocyclic Chemistry, 57(11), 3907-3917. Silva, D., Diniz-Neto, H., Cordeiro, L., Silva-Neta, M., Silva, S., Andrade-Júnior, F. et al. (2020) (R)-(+)-β-Citronellol and (S)-(−)-β-citronellol in combination with amphotericin B against Candida spp. International Journal of Molecular Sciences, 21(5), 1785. Silva, D.R., Sardi, J.D.C.O., Freires, I.A., Silva, A.C.B. & Rosalen, P.L. (2019) In silico approaches for screening molecular targets in Candida albicans: a proteomic insight into drug discovery and development. European Journal of Pharmacology, 842, 64-69. Silva, K.V., Lima, M.I., Cardoso, G.N., Santos, A.S., Silva, G.S. & Pereira, F.O. (2017) Inibitory effects of linalool on fungal pathogenicity of clinical isolates of Microsporumcanis and Microsporumgypseum. Mycoses, 60(6), 387-393. Silva, S., Negri, M., Henriques, M., Oliveira, R., Williams, D.W. & Azeredo, J. (2011) Adherence and biofilm formation of non-Candida albicans Candida species. Trends in Microbiology, 19(5), 241-247. Souza, H.D., de Sousa, R.P., Lira, B.F., Vilela, R.F., Borges, N.H., Siqueira-Junior, J.P.D. et al. (2019) Synthesis, in silico study and antimicrobial evaluation of new selenoglycolicamides. Journal of the Brazilian Chemical Society, 30, 188-197. Soyer, Z. & Eraç, B. (2007) Evaluation of antimicrobial activities of some 2 (3H)-benzoxazolone derivatives. Fabad Journal of Pharmaceutical Sciences, 32(4), 167. Sun, Q., Xiong, K., Yuan, Y., Yu, J., Yang, L., Shen, C. et al. (2020) Inhibiting fungal echinocandin resistance by small-molecule disruption of geranylgeranyltransferase type I activity. Antimicrobial Agents and Chemotherapy, 64(2), 02046-19. Thomsen, R. & Christensen, M.H. (2006) MolDock: a new technique for high-accuracy molecular docking. Journal of Medicinal Chemistry, 49, 3315-3321. Torres-Guerrero, E. & Arenas, R. (2017) Candida onychomycosis. In: Tosti, A., Vlahovic, T. & Arenas, R. (Eds.) Onychomycosis. Cham: Springer. Vila, T.V.M., Quintanilha, N.S. & Rozental, S. (2015) Miltefosine is effective against Candida albicans and Fusarium oxysporum nail biofilms in vitro. Journal of Medical Microbiology, 64(11), 1436-1449. Vila, T.V.M., Rozental, S. & De Sá Guimarães, C.M.D. (2015) A new model of in vitro fungal biofilms formed on human nail fragments allows reliable testing of laser and light therapies against onychomycosis. Lasers in Medical Science, 30(3), 1031-1039. Whitlow, M., Howard, A.J., Stewart, D., Hardman, K.D., Kuyper, L.F., Baccanari, D.P. et al. (1997) X-ray crystallographic studies of Candida albicans dihydrofolate reductase: high resolution structures of the holoenzyme and an inhibited ternary complex. The Journal of Biological Chemistry, 272(48), 30289-30298. Yadav, S., Lim, S.M., Ramasamy, K., Vasudevan, M., Ali Shan, A.S., Mathur, A. et al. (2018) Synthesis and evaluation of antimicrobial, antitubercular and anticancer activities of 2-(1-benzoyl-1H-benzo[d]imidazol-2-ylthio)-N-substituted acetamides. Chemistry Central Journal, 12(1), 1-14. Yurttaş, L., Kubilay, A., Evren, A.E., Kısacık, İ. & Karaca Gençer, H. (2020) Synthesis of some novel 3, 4, 5-trisubstituted Triazole derivatives bearing quinoline ring and evaluation of their antimicrobial activity. Phosphorus, Sulfur and Silicon and the Related Elements, 195(9), 767-773. |
| معلومات مُعتمدة: | CNPq; CAPES; Federal University of Paraíba |
| فهرسة مساهمة: | Keywords: antibiofilm; onychomycosis; resistance; synthetic drug |
| المشرفين على المادة: | 0 (Antifungal Agents) 8VZV102JFY (Fluconazole) |
| تواريخ الأحداث: | Date Created: 20220218 Date Completed: 20220415 Latest Revision: 20220415 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1111/jam.15498 |
| PMID: | 35179275 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1365-2672 |
|---|---|
| DOI: | 10.1111/jam.15498 |