In vitro inhibition effect of sulphonylhydrazones against Malassezia furfur

Öz

Purpose: In this study, the in-vitro antifungal activity of previously synthesized compounds, including methanesulfonic acid hydrazide (I) and its derivatives 3.5-ditertbutylsalicylaldehyde methanesulfonylhydrazone (II), 3-tertbutylsalicylaldehyde methanesulfonylhydrazone (III), and 5-bromosalicylaldehyde methanesulfonylhydrazone (IV), was investigated for the first time against Malassezia furfur isolates.
Materials and methods: The study included 16 M. furfur isolated from patients' skin, as well as a reference strain M.furfur CBS 1878 (ATCC 14521). In the liquid microdilution test, the new sulphonylhydrazones and fluconazole were placed in flat-bottom microtitration plate wells at a concentration range of 0.25-128 μg/ml in 100 μl suspensions. A modified optimal medium was prepared. The medium and yeast suspensions were distributed in 100 μL aliquots into the microtitration plate wells, with negative and positive controls for each sample. Minimum inhibition concentration (MIC) was evaluated by visual reading.
Results: High antifungal activity was observed in compound III, while low antifungal activity was detected in the other compounds.
Conclusion: The method used is simple and reproducible, and the sulphonylhydrazones have antifungal activity against M. furfur.

Anahtar Kelimeler

• Sulfonylhydrazone
• Malassezia furfur
• antifungal activity

Etik Beyan

Permission was obtained from ****** University Non-Interventional Clinical Research Ethics Committee for the study (E.353841 - 06/04/2023).

Malassezia furfur'a karşı sülfonilhidrazonların in vitro inhibisyon etkisi

Öz

Amaç: Bu çalışmada, metan sülfonik asit hidrazid (I) ve türevleri 3,5-ditertbutilsalisilaldehit metan sülfonilhidrazon (II), 3-tert-butilsalisilaldehit metansülfonilhidrazon (III) ve 5-bromosalisilaldehit metansülfonilhidrazon (IV) gibi daha önce sentezlenmiş bileşiklerin in vitro antifungal aktivitesi, Malassezia furfur izolatlarına karşı ilk kez araştırılmıştır.
Gereç ve yöntem: Çalışmaya, hastaların derisinden izole edilen 16 M. furfur ve bir referans suşu M.furfur CBS 1878 (ATCC 14521) dahil edildi. Sıvı mikrodilüsyon testinde, yeni sülfonil hidrazonlar ve flukonazol, 100 μl süspansiyonlarda 0,25-128 μg/ml konsantrasyon aralığında düz tabanlı mikrotitrasyon plakası kuyucuklarına yerleştirildi. Modifiye edilmiş optimal ortam hazırlandı. Ortam ve maya süspansiyonları, her numune için negatif ve pozitif kontrollerle birlikte 100 μL'lik alikvotlar halinde mikro titrasyon plakası kuyucuklarına dağıtıldı. Minimum inhibisyon konsantrasyonu (MIC) görsel okuma ile değerlendirildi.
Bulgular: Bileşik III'te yüksek antifungal aktivite gözlenirken, diğer bileşiklerde düşük antifungal aktivite tespit edildi.
Sonuç: Kullanılan yöntem basit ve tekrarlanabilir olup, sülfonil hidrazonlar M. furfur'a karşı antifungal aktiviteye sahiptir.

Anahtar Kelimeler

• Sülfonilhidrazon
• Malassezia furfur
• antifungal

Etik Beyan

Çalışma için Pamukkale Üniversitesi Girişimsel Olmayan Klinik Araştırmalar Etik Kurulu’ndan izin alınmıştır (E.353841 - 06/04/2023).

Kaynakça

1. Theelen, B., Cafarchia, C., Gaitanis, G., Bassukas, I. D., Boekhout, T., & Dawson, T. L., Jr (2018). Malassezia ecology, pathophysiology, and treatment. Medical mycology, 56(suppl_1), S10–S25. https://doi.org/10.1093/mmy/myx134
2. Hobi, S., Cafarchia, C., Romano, V., & Barrs, V. R. (2022). Malassezia: Zoonotic Implications, Parallels and Differences in Colonization and Disease in Humans and Animals. Journal of fungi (Basel, Switzerland), 8(7), 708. https://doi.org/10.3390/jof8070708
3. Ugochukwu, I. C. I., Rhimi, W., Chebil, W., Rizzo, A., Tempesta, M., Giusiano, G., Tábora, R. F. M., Otranto, D., & Cafarchia, C. (2023). Part 1: Understanding the role of Malassezia spp. in skin disorders: Malassezia yeasts as commensal or pathogenic organisms of human and animal skin. Expert review of anti-infective therapy, 21(12), 1327–1338. https://doi.org/10.1080/14787210.2023.2276367
4. Rhimi, W., Theelen, B., Boekhout, T., Otranto, D., & Cafarchia, C. (2020). Malassezia spp. Yeasts of Emerging Concern in Fungemia. Frontiers in cellular and infection microbiology, 10, 370. https://doi.org/10.3389/fcimb.2020.00370
5. Chen, I. T., Chen, C. C., Huang, H. C., & Kuo, K. C. (2020). Malassezia furfur Emergence and Candidemia Trends in a Neonatal Intensive Care Unit During 10 Years: The Experience of Fluconazole Prophylaxis in a Single Hospital. Advances in neonatal care : official journal of the National Association of Neonatal Nurses, 20(1), E3–E8. https://doi.org/10.1097/ANC.0000000000000640
6. Ehemann, K., Contreras, A., & Celis-Ramírez, A. M. (2023). In vitro sensitivity of Malassezia furfur isolates from HIV-positive and negative patients to antifungal agents. Sensibilidad in vitro a antifúngicos de aislamientos de Malassezia furfur de pacientes positivos y negativos para HIV. Biomedica : revista del Instituto Nacional de Salud, 43(Sp. 1), 120–131. https://doi.org/10.7705/biomedica.6871
7. Rojas, F. D., Sosa, M.deL., Fernández, M. S., Cattana, M. E., Córdoba, S. B., & Giusiano, G. E. (2014). Antifungal susceptibility of Malassezia furfur, Malassezia sympodialis, and Malassezia globosa to azole drugs and amphotericin B evaluated using a broth microdilution method. Medical mycology, 52(6), 641–646. https://doi.org/10.1093/mmy/myu010
8. Bonardi, A., Gratteri, P., Nocentini. A. (2019). Carbonic anhydrases from pathogens: Fungal carbonic anhydrases and their inhibitors as potential antifungal agents. Carbonic Anhydrases.: Academic Press; https://doi.org//10.1016/B978-0-12-816476-1.00019-8

9. De Luca, V., Carginale, V., Supuran, C. T., & Capasso, C. (2022). The gram-negative bacterium Escherichia coli as a model for testing the effect of carbonic anhydrase inhibition on bacterial growth. Journal of enzyme inhibition and medicinal chemistry, 37(1), 2092–2098. https://doi.org/10.1080/14756366.2022.2101644
10. Capasso, C., & Supuran, C. T. (2015). Bacterial, fungal and protozoan carbonic anhydrases as drug targets. Expert opinion on therapeutic targets, 19(12), 1689–1704. https://doi.org/10.1517/14728222.2015.1067685
11. Popiołek Ł. (2021). The bioactivity of benzenesulfonyl hydrazones: A short review. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 141, 111851. https://doi.org/10.1016/j.biopha.2021.111851
12. Nocentini, A., Vullo, D., Bartolucci, G., & Supuran, C. T. (2016). N-Nitrosulfonamides: A new chemotype for carbonic anhydrase inhibition. Bioorganic & medicinal chemistry, 24(16), 3612–3617. https://doi.org/10.1016/j.bmc.2016.05.072
13. Verma, G., Marella, A., Shaquiquzzaman, M., Akhtar, M., Ali, M. R., & Alam, M. M. (2014). A review exploring biological activities of hydrazones. Journal of pharmacy & bioallied sciences, 6(2), 69–80. https://doi.org/10.4103/0975-7406.129170
14. Angiolella, L., Carradori, S., Maccallini, C., Giusiano, G., & Supuran, C. T. (2017). Targeting Malassezia species for Novel Synthetic and Natural Antidandruff Agents. Current medicinal chemistry, 24(22), 2392–2412. https://doi.org/10.2174/0929867324666170404110631
15. Supuran, C. T., & Capasso, C. (2021). A Highlight on the Inhibition of Fungal Carbonic Anhydrases as Drug Targets for the Antifungal Armamentarium. International journal of molecular sciences, 22(9), 4324. https://doi.org/10.3390/ijms22094324
16. Uzun, D., Erdoğdu, E., Balaban Gündüzalp, A., Özmen Özdemir, Ümmühan, Öztürk, A., Özbek, N., Kaya, K., & Abdulmajet, O. (2021). New sulfonylhydrazones containing methane sulfonic acid hydrazıde havıng human anticarbonic anhydrase and antimicrobıal activıty: synthesis, spectroscopic characterization, electrochemical properties, and biological activıties. Macedonian Journal of Chemistry and Chemical Engineering, 40(2), 181–196. https://doi.org/10.20450/mjcce.2021.2416
17. Ergin, Ç., Öner, S. Z., Özkan, B., Onaç, C., Gümral, R., Okul, M., & Şengül, M. (2023). Polipropilen Membran Üzerinde Malassezia furfur Biyofilm Oluşumunun Değerlendirilmesi. Mikrobiyoloji bulteni, 57(3), 432–443. https://doi.org/10.5578/mb.20239935
18. Leong, C., Buttafuoco, A., Glatz, M., & Bosshard, P. P. (2017). Antifungal Susceptibility Testing of Malassezia spp. with an Optimized Colorimetric Broth Microdilution Method. Journal of clinical microbiology, 55(6), 1883–1893. https://doi.org/10.1128/JCM.00338-17
19. Benkova, M., Soukup, O., & Marek, J. (2020). Antimicrobial susceptibility testing: currently used methods and devices and the near future in clinical practice. Journal of applied microbiology, 129(4), 806–822. https://doi.org/10.1111/jam.14704
20. Gajic, I., Kabic, J., Kekic, D., Jovicevic, M., Milenkovic, M., Mitic Culafic, D., Trudic, A., Ranin, L., & Opavski, N. (2022). Antimicrobial Susceptibility Testing: A Comprehensive Review of Currently Used Methods. Antibiotics (Basel, Switzerland), 11(4), 427. https://doi.org/10.3390/antibiotics11040427
21. Erkekoğlu, P. ve Baydar, T. (2021). Güncel İn Vitro Sitotoksisite Testleri. Hacettepe Üniversitesi Eczacılık Fakültesi Dergisi, 41(1), 45-63. https://izlik.org/JA33NM29TY
22. Ibáñez, D., Izquierdo-Bote, D., Pérez-Junquera, A., González-García, MB, Hernandez-Santos, D. &Fanjul-Bolado, P. (2020). Resazurin-resorufin florojenik sisteminin Raman ve floresans spektroelektrokimyasal izlenmesi. Boyalar ve Pigmentler , 172 , 107848. https://doi.org/10.1016/j.dyepig.2019.107848
23. Cafarchia, C., Iatta, R., Immediato, D., Puttilli, M. R., & Otranto, D. (2015). Azole susceptibility of Malassezia pachydermatis and Malassezia furfur and tentative epidemiological cut-off values. Medical mycology, 53(7), 743–748. https://doi.org/10.1093/mmy/myv049
24. Rhimi, W., Chebil, W., Ugochukwu, I. C. I., Babba, H., Otranto, D., & Cafarchia, C. (2022). Comparison of virulence factors and susceptibility profiles of Malassezia furfur from pityriasis versicolor patients and bloodstream infections of preterm infants. Medical mycology, 61(1), myad003. https://doi.org/10.1093/mmy/myad003
25. Rojas, F. D., Sosa, M. L. Á., Latorre, W., Mussin, J., Alegre, L., & Giusiano, G. (2022). Malassezia species: the need to establish epidemiological cutoff values. Medical mycology, 60(8), myac048. https://doi.org/10.1093/mmy/myac048
26. Galvis-Marín, J. C., Celis-Ramírez, A. M., Tabares-Villa, F. A., Zuluaga-Vélez, A., & Sepúlveda-Arias, J. C. (2025). Characterisation of Antifungal Resistance to Azoles in Colombian Isolates of Malassezia spp. Mycoses, 68(9), e70112. https://doi.org/10.1111/myc.70112
27. Abdoli, M., De Luca, V., Capasso, C., Supuran, C. T., & Žalubovskis, R. (2022). Benzenesulfonamides Incorporating Hydantoin Moieties Effectively Inhibit Eukaryoticand Human Carbonic Anhydrases. International journal of molecular sciences, 23(22), 14115. https://doi.org/10.3390/ijms232214115
28. De Luca, V., Angeli, A., Mazzone, V., Adelfio, C., Carta, F., Selleri, S., Carginale, V., Scaloni, A., Supuran, C. T., & Capasso, C. (2021). Inhibitory Effects of Sulfonamide Derivatives on the β-Carbonic Anhydrase (MpaCA) from Malassezia pachydermatis, a Commensal, Pathogenic Fungus Present in Domestic Animals. International journal of molecular sciences, 22(22), 12601. https://doi.org/10.3390/ijms222212601 1
29. Del Prete, S., Angeli, A., Ghobril, C., Hitce, J., Clavaud, C., Marat, X., Supuran, C. T., & Capasso, C. (2020). Sulfonamide Inhibition Profile of the β-Carbonic Anhydrase from Malassezia restricta, An Opportunistic Pathogen Triggering Scalp Conditions. Metabolites, 10(1), 39. https://doi.org/10.3390/metabo10010039
30. Billamboz, M., & Jawhara, S. (2023). Anti-Malassezia Drug Candidates Based on Virulence Factors of Malassezia-Associated Diseases. Microorganisms, 11(10), 2599. https://doi.org/10.3390/microorganisms11102599
31. Aydin, M., Ozturk, A., Duran, T., Ozmen, U. O., Sumlu, E., Ayan, E. B., & Korucu, E. N. (2023). In vitro antifungal and antibiofilm activities of novel sulfonyl hydrazone derivatives against Candida spp. Journal de mycologie medicale, 33(1), 101327. https://doi.org/10.1016/j.mycmed.2022.101327