1887

Abstract

Onychomycosis infections currently show a significant increase, affecting about 10 % of the world population. is the main agent responsible for about 80 % of the reported infections. The clinical cure for onychomycosis is extremely difficult and effective new antifungal therapy is needed.

onychomycosis models using porcine hooves can be an excellent alternative for evaluating the efficacy of new anti-dermatophytic agents in a nail lacquer.

Evaluation of the effectiveness of a nail lacquer containing a quinoline derivative on an onychomycosis model using porcine hooves, as well as the proposal of a plausible antifungal mechanism of this derivative against dermatophytic strains.

The action mechanism of a quinoline derivative was evaluated through the sorbitol protection assay, exogenous ergosterol binding, and the determination of the dose-response curves by time-kill assay. Scanning electron microscopy evaluated the effect of the derivative in the fungal cells. The efficacy of a quinoline-derivative nail lacquer on an onychomycosis model using porcine hooves was evaluated as well.

The quinoline derivative showed a time-dependent fungicidal effect, demonstrating reduction and damage in the morphology of dermatophytic hyphae. In addition, the onychomycosis model was effective in the establishment of infection by .

Treatment with the quinoline-derivative lacquer showed a significant inhibitory effect on strain in this infection model. Finally, the compound presents high potential for application in a formulation such as nail lacquer as a possible treatment for dermatophytic onychomycosis.

Funding
This study was supported by the:
  • FAPERGS (Award 16/2551-0000517-6)
    • Principle Award Recipient: AlexandreMeneghello Fuentefria
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2021-01-27
2024-04-25
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References

  1. Hayette M-P, Sacheli R. Dermatophytosis, trends in epidemiology and diagnostic approach. Curr Fungal Infect Rep 2015; 9:164–179 [View Article]
    [Google Scholar]
  2. Gnat S, Łagowski D, Nowakiewicz A, Zięba P. The host range of dermatophytes, it is at all possible? Phenotypic evaluation of the keratinolytic activity of Trichophyton verrucosum clinical isolates. Mycoses 2018; 2018:1–10
    [Google Scholar]
  3. Vlahovic TC. Onychomycosis. Clin Podiatr Med Surg 2016; 33:305–318 [View Article]
    [Google Scholar]
  4. Lavorato FG, Guimarães DA, Premazzi MG, Piñeiro-Maceira JM, Bernardes-Engemann AR et al. Performance of mycology and histopathology tests for the diagnosis of toenail onychomycosis due to filamentous fungi: dermatophyte and non-dermatophyte moulds. Mycoses 2017; 60:587–593 [View Article][PubMed]
    [Google Scholar]
  5. Sleven R, Lanckacker E, Boulet G, Delputte P, Maes L et al. Development of a novel in vitro onychomycosis model for the evaluation of topical antifungal activity. J Microbiol Methods 2015; 112:73–75 [View Article][PubMed]
    [Google Scholar]
  6. Garcia Garces H, Hrycyk MF, Giacobino J, Capela Machado G, Domingos Arantes T et al. Molecular identification and phylogenetical analysis of dermatophyte fungi from Latin America. Mycoses 2016; 59:787–797 [View Article][PubMed]
    [Google Scholar]
  7. Anupama A. Isolation and identification of dermatophytes from clinical samples – one year study. Int.J.Curr.Microbiol.App.Sci 2017; 6:1276–1281 [View Article]
    [Google Scholar]
  8. Pihet M, Le Govic Y. Reappraisal of conventional diagnosis for dermatophytes. Mycopathologia 2017; 182:169–180 [View Article][PubMed]
    [Google Scholar]
  9. Shemer A, Babaev M. Fungal infections (onychomycosis, tinea pedis, tinea cruris, tinea capitis, tinea manuum, tinea corporis, different Candida infections, and pityriasis versicolor) and mycological laboratory analyses. In Tur E, Maibach H. (editors) Gender and Dermatology Springer; 2018 pp 235–242
    [Google Scholar]
  10. Zhan P, Dukik K, Li D, Sun J, Stielow JB et al. Phylogeny of dermatophytes with genomic character evaluation of clinically distinct Trichophyton rubrum and T. violaceum . Stud Mycol 2018; 89:153–175 [View Article][PubMed]
    [Google Scholar]
  11. Martínez E, Ameen M, Tejada D, Arenas R. Microsporum spp. onychomycosis: disease presentation, risk factors and treatment responses in an urban population. Braz J Infect Dis 2014; 18:181–186 [View Article][PubMed]
    [Google Scholar]
  12. Fike JM, Kollipara R, Alkul S, Stetson CL. Case report of onychomycosis and tinea corporis due to Microsporum gypseum . J Cutan Med Surg 2018; 22:94–96 [View Article][PubMed]
    [Google Scholar]
  13. Miron D, Cornelio R, Troleis J, Mariath J, Zimmer AR et al. Influence of penetration enhancers and molecular weight in antifungals permeation through bovine hoof membranes and prediction of efficacy in human nails. Eur J Pharm Sci 2014; 51:20–25 [View Article][PubMed]
    [Google Scholar]
  14. Täuber A, Müller-Goymann CC. In vitro permeation and penetration of ciclopirox olamine from poloxamer 407-based formulations--comparison of isolated human stratum corneum, bovine hoof plates and keratin films. Int J Pharm 2015; 489:73–82 [View Article][PubMed]
    [Google Scholar]
  15. McAuley WJ, Jones SA, Traynor MJ, Guesné S, Murdan S et al. An investigation of how fungal infection influences drug penetration through onychomycosis patient's nail plates. Eur J Pharm Biopharm 2016; 102:178–184 [View Article][PubMed]
    [Google Scholar]
  16. Afzal O, Kumar S, Haider MR, Ali MR, Kumar R et al. A review on anticancer potential of bioactive heterocycle quinoline. Eur J Med Chem 2015; 97:871–910 [View Article][PubMed]
    [Google Scholar]
  17. Singh S, Kaur G, Mangla V, Gupta MK. Quinoline and quinolones: promising scaffolds for future antimycobacterial agents. J Enzyme Inhib Med Chem 2015; 30:492–504 [View Article][PubMed]
    [Google Scholar]
  18. Kadri D, Crater AK, Lee H, Solomon VR, Ananvoranich S. The potential of quinoline derivatives for the treatment of Toxoplasma gondii infection. Exp Parasitol 2014; 145:135–144 [View Article][PubMed]
    [Google Scholar]
  19. Wen X, Wang S-B, Liu D-C, Gong G-H, Quan Z-S. Synthesis and evaluation of the anti-inflammatory activity of quinoline derivatives. Med Chem Res 2015; 24:2591–2603 [View Article]
    [Google Scholar]
  20. Liberto NA, Simões JB, de Paiva Silva S, da Silva CJ, Modolo LV et al. Quinolines: microwave-assisted synthesis and their antifungal, anticancer and radical scavenger properties. Bioorg Med Chem 2017; 25:1153–1162 [View Article][PubMed]
    [Google Scholar]
  21. El Shehry MF, Ghorab MM, Abbas SY, Fayed EA, Shedid SA et al. Quinoline derivatives bearing pyrazole moiety: synthesis and biological evaluation as possible antibacterial and antifungal agents. Eur J Med Chem 2018; 143:1463–1473 [View Article][PubMed]
    [Google Scholar]
  22. Teng P, Li C, Peng Z, Anne Marie V, Nimmagadda A et al. Facilely accessible quinoline derivatives as potent antibacterial agents. Bioorg Med Chem 2018; 26:3573–3579 [View Article][PubMed]
    [Google Scholar]
  23. da Rosa Monte Machado G, Diedrich D, Ruaro TC, Zimmer AR, Lettieri Teixeira M et al. Quinolines derivatives as promising new antifungal candidates for the treatment of candidiasis and dermatophytosis. Braz J Microbiol 2020; 51:1691–1701 [View Article][PubMed]
    [Google Scholar]
  24. Reichl S, Müller-Goymann CC. Infected nail plate model made of human hair keratin for evaluating the efficacy of different topical antifungal formulations against Trichophyton rubrum in vitro . Eur J Pharm Biopharm 2013; 84:599–605 [View Article][PubMed]
    [Google Scholar]
  25. Thatai P, Sapra B. Transungual delivery: deliberations and creeds. Int J Cosmet Sci 2014; 36:398–411 [View Article][PubMed]
    [Google Scholar]
  26. Dai T, Tegos GP, Rolz-Cruz G, Cumbie WE, Hamblin MR. Ultraviolet C inactivation of dermatophytes: implications for treatment of onychomycosis. Br J Dermatol 2008; 158:1239–1246 [View Article][PubMed]
    [Google Scholar]
  27. Clinical and Laboratory Standards Institute (CLSI) Reference Method for Broth Dilution Antifungal Susceptibility Testing of Filamentous fungi; Approved Standard, 2ed ed. Wayne, PA: CLSI Document; 2008 pp M38–A2
    [Google Scholar]
  28. R M Machado Gda, Pippi B, Dalla Lana DF, Amaral APS, Teixeira ML et al. Reversal of fluconazole resistance induced by a synergistic effect with Acca sellowiana in Candida glabrata strains. Pharm Biol 2016; 54:2410–2419 [View Article][PubMed]
    [Google Scholar]
  29. Escalante A, Gattuso M, Pérez P, Zacchino S. Evidence for the mechanism of action of the antifungal phytolaccoside B isolated from Phytolacca Tetramera Hauman. J Nat Prod 2008; 71:1720–1725 [View Article][PubMed]
    [Google Scholar]
  30. Pippi B, Reginatto P, Machado GdaRM, Bergamo VZ, Lana DFD et al. Evaluation of 8-hydroxyquinoline derivatives as hits for antifungal drug design. Med Mycol 2017; 55:763–773 [View Article][PubMed]
    [Google Scholar]
  31. Joubert L-M, Ferreira JAG, Stevens DA, Cegelski L. Aspergillus fumigatus biofilms: a comparison of processing techniques for scanning electron microscopy of fungal mycelium and extracellular matrix. Microsc Microanal 2015; 21:935–936 [View Article]
    [Google Scholar]
  32. Maciel Quatrin P, Flores Dalla Lana D, Andrzejewski Kaminski TF, Meneghello Fuentefria A, Quatrin PM. Fungal infection models: current progress of ex vivo methods. Mycoses 2019; 62:860–873 [View Article][PubMed]
    [Google Scholar]
  33. Chung P-Y, Bian Z-X, Pun H-Y, Chan D, Chan AS-C et al. Recent advances in research of natural and synthetic bioactive quinolines. Future Med Chem 2015; 7:947–967 [View Article][PubMed]
    [Google Scholar]
  34. Parhizgar AR, Tahghighi A. Introducing new antimalarial analogues of chloroquine and amodiaquine: a narrative review. Iran J Med Sci 2017; 42:115–128[PubMed]
    [Google Scholar]
  35. Sullivan DJ. Quinolines block every step of malaria heme crystal growth. Proc Natl Acad Sci U S A 2017; 114:7483–7485 [View Article][PubMed]
    [Google Scholar]
  36. Cholo MC, Mothiba MT, Fourie B, Anderson R. Mechanisms of action and therapeutic efficacies of the lipophilic antimycobacterial agents clofazimine and bedaquiline. J Antimicrob Chemother 2017; 72:338–353 [View Article][PubMed]
    [Google Scholar]
  37. Coimbra ES, Antinarelli LMR, Silva NP, Souza IO, Meinel RS et al. Quinoline derivatives: synthesis, leishmanicidal activity and involvement of mitochondrial oxidative stress as mechanism of action. Chem Biol Interact 2016; 260:50–57 [View Article][PubMed]
    [Google Scholar]
  38. El-Gamal KM, El-Morsy AM, Saad AM, Eissa IH, Alswah M. Synthesis, docking, QSAR, ADMET and antimicrobial evaluation of new quinoline-3-carbonitrile derivatives as potential DNA-gyrase inhibitors. J Mol Struct 2018; 1166:15–33 [View Article]
    [Google Scholar]
  39. Collin F, Karkare S, Maxwell A. Exploiting bacterial DNA gyrase as a drug target: current state and perspectives. Appl Microbiol Biotechnol 2011; 92:479–497 [View Article][PubMed]
    [Google Scholar]
  40. Elsayed MMA. Development of topical therapeutics for management of onychomycosis and other nail disorders: a pharmaceutical perspective. J Control Release 2015; 199:132–144 [View Article][PubMed]
    [Google Scholar]
  41. Ghannoum M, Sevin K, Sarkany M. Amorolfine 5% nail lacquer exhibits potent antifungal activity compared to three acid-based devices indicated for the treatment of onychomycosis: an in vitro nail penetration assay. Dermatol Ther 2016; 6:69–75 [View Article]
    [Google Scholar]
  42. Campoy S, Adrio JL. Antifungals. Biochem Pharmacol 2017; 133:86–96 [View Article][PubMed]
    [Google Scholar]
  43. Sleven R, Lanckacker E, Delputte P, Maes L, Cos P. Evaluation of topical antifungal products in an in vitro onychomycosis model. Mycoses 2016; 59:327–330 [View Article][PubMed]
    [Google Scholar]
  44. Kano R, Hsiao Y-H, Han HS, Chen C, Hasegawa A et al. Resistance mechanism in a terbinafine-resistant strain of Microsporum canis . Mycopathologia 2018; 183:623–627 [View Article][PubMed]
    [Google Scholar]
  45. Sigurgeirsson B. Onychomycosis. In Ólafsson JH, Hay RJ. (editors) Antibiotic and Antifungal Therapies in Dermatology Springer; 2016 pp 203–289
    [Google Scholar]
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