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Current Research and New Perspectives in Antifungal Drug Development

  • Iulian Oltu
  • Liliana Cepoi
  • Valeriu Rudic
  • Ludmila Rudi
  • Tatiana Chiriac
  • Ana Valuta
  • Svetlana CodreanuEmail author
Part of the Advances in Experimental Medicine and Biology book series


In recent times, fungi are becoming more and more active as causal agents of human infections, which is primarily determined by the growing number of people with severe immunosuppression. Thus, the problems of elucidating the mechanisms of action of antifungal preparations, highlighting ways to obtain resistance to their action and research strategies aimed at discovering new compounds with antifungal properties remain the focus of contemporary biomedicine and pharmaceutics. This paper reviews the recent achievements in antifungal drug development and focuses on new natural antifungal remedies with a noticeable effect on pathogens with minimal adverse effects on the host organism.


Drug resistance Natural antifungals Oxidative stress Pathogenic fungi Spirulina extracts 


Compliance with Ethical Standards

Conflict of Interest: Author Iulian Oltu declares that he has no conflict of interest. Author Liliana Cepoi declares that she has no conflict of interest. Author Valeriu Rudic declares that he has no conflict of interest. Author Ludmila Rudi declares that she has no conflict of interest. Author Tatiana Chiriac declares that she has no conflict of interest. Author Ana Valuta declares that she has no conflict of interest. Author Svetlana Codreanu declares that she has no conflict of interest.

Ethical Approval: This article does not contain any studies with human participants or animals performed by any of the authors.


  1. Abed R, Dobretsov S, Sudesh K (2009) Applications of cyanobacteria in biotechnology. J Appl Microbiol 106(1):1–12Google Scholar
  2. Ansari M, Anurag A, Fatima Z et al (2013) Natural phenolic compounds: a potential antifungal agent. In: Mendez-Vilas A (ed) Microbial pathogens and strategies for combating them: science, technology and education. Formatex Research Center, Badajoz, pp 1189–1195Google Scholar
  3. Arif T, Bhosale JD, Kumar N et al (2009) Natural products – antifungal agents derived from plants. J Asian Nat Prod Res 11(7):621–638Google Scholar
  4. Baddley JW, Winthrop KL, Patkar NM, Delzell E, Beukelman T, Xie F, Chen L, Curti JR (2011) Geographic distribution of endemic fungal infections among older persons, United States. Emerg Infect Dis 17(9):1664–1669Google Scholar
  5. Baghi N, Shokohi T, Badali H et al (2016) In vitro activity of new azoles luliconazole and lanoconazole compared with ten other antifungal drugs against clinical dermatophyte isolates. Med Mycol 54(7):757–763Google Scholar
  6. Battah MG, Ibrahim HAH, El-Naggar MM et al (2014) Antifungal agent from Spirulina maxima: extraction and characterization. GJP 8(2):228–236Google Scholar
  7. Blyth C (2012) Antifungal azoles: old and new. Pediatr Infect Dis J 30(6):506–507Google Scholar
  8. Brown G, Denning DW, Cow NA et al (2012) Hidden killers: human fungal infections. Sci Transl Med 4(165):165rv113Google Scholar
  9. Brown EM, McTaggart LR, Dunn D, Pszczolko E, Tsui KG, Morris SK, Stephens D, Kus JV, Richardson SE (2018) Epidemiology and geographic distribution of blastomycosis, histoplasmosis, and coccidioidomycosis, Ontario, Canada, 1990-2015. Emerg Infect Dis 24(7):1257–1266Google Scholar
  10. Burja A et al (2001) Marine cyanobacteria—a prolific source of natural products. Tetrahedron 57(46):9347–9377Google Scholar
  11. Caggiano G (2012) Fungal infection in patients of paediatric age. In: Oner O (ed) Contemporary pediatrics. Intech, Rijeka, pp 385–402Google Scholar
  12. Castillo F, Hernandez D, Gallegos G et al (2012) Antifungal properties of bioactive compounds from plants. In: Dhanasekaran D, Thajuddin N, Annamalai S (eds) Fungicides for plant and animal diseases, Intech, pp 81–106Google Scholar
  13. Chandrasekar P (2011) Management of invasive fungal infections: a role for polyenes. J Antimicrob Chemother 66(3):457–465Google Scholar
  14. Chowdhary A, Agarwal K, Meis JF (2016) Filamentous fungi in respiratory infections. What lies beyond aspergillosis and mucormycosis? PLoS Pathog 12(4):e1005491Google Scholar
  15. Cowen L, Sanglard D, Howard SJ et al (2014) Mechanisms of antifungal drug resistance. Cold Spring Harb Perspect Med 5(7):a019752Google Scholar
  16. Cretton S, Dorsaz S, Azzollini A et al (2016) Antifungal quinoline alkaloids from Waltheria indica. J Nat Prod 79(2):300–307Google Scholar
  17. Davis S (2005) An overview of the antifungal properties of allicin and its breakdown products – the possibility of a safe and effective antifungal prophylactic. Mycoses 48(2):95–100Google Scholar
  18. Debourgogne A, Dorin J, Machouart M (2016) Emerging infections due to filamentous fungi in humans and animals: only the tip of the iceberg? Environ Microbiol Rep 8(3):332–342Google Scholar
  19. Gatto MA, Sanzani SM, Tradia P et al (2013) Antifungal activity of total and fractionated phenolic extracts from two wild edible herbs. Nat Sci 5(8):895–902Google Scholar
  20. Grover N (2010) Echinocandins: a ray of Hope in antifungal drug therapy. Indian J Pharmacol 42(1):9–11Google Scholar
  21. Harrison B, Hashemi J, Bibi M et al (2014) A tetraploid intermediate precedes aneuploid formation in yeasts exposed to fluconazole. PLoS Biology 12:e1001815Google Scholar
  22. Havlickova B, Czaika V, Friedrich M (2008) Epidemiological trends in skin mycoses worldwide. Mycoses 51(Suppl. 4):2–15Google Scholar
  23. Kauffman CA, Pappas PG, Sobel JD, Dismukes WE (eds) (2011) Essential of clinical mycology. Springer, New York/Dordrecht/Heidelberg/London. 542 pGoogle Scholar
  24. Kshetrimayum M, Kant M (2016) Antimicrobial activities of freshwater cyanobacterium, Nostoc sp. from Tamdil Wetland of Mizoram, India: an identification of bioactive compounds by GC-MS. Int J Pharm Sci Res 2(5):199–208Google Scholar
  25. Kumar V, Usmani SK, Shrivastava JN (2009) Antifungal activity of Spirulina platensis (Geitler) against some human pathogenic fungi. Int J Plant Res 22(2):83–89Google Scholar
  26. Latté K, Kolodziej H (2000) Antifungal effects of hydrolysable tannins and related compounds on dermatophytes, mould fungi and yeasts. Z Naturforsch C 55(5–6):467–472Google Scholar
  27. Lehrnbecher T, Frank C, Engels K et al (2010) Trends in the postmortem epidemiology of invasive infections at a university hospital. J Infect 61(3):259–265Google Scholar
  28. Marichal P, Vanden Bossche H, Odds FC et al (1997) Molecular biological characterization of an azole-resistant Candida glabrata isolate. Antimicrob Agents Chemother 41(10):2229–2237Google Scholar
  29. Mazu TK, Bricker BA, Flores-Rozan H et al (2016) The mechanistic targets of antifungal agents: an overview. Mini-Rev Med Chem 16(7):555–578Google Scholar
  30. Miron D, Battisti F, Silca F et al (2014) Antifungal activity and mechanism of action of monoterpenes against dermatophytes and yeasts. Rev Bras Farm 24(6):660–667Google Scholar
  31. Moraes De Souza M, Prietto L, Ribeiro AC et al (2011) Assessment of the antifungal activity of spirulina platensis phenolic extract against Aspergillus flavus. Ciênc Agrotecnol 35(6):1050–1058Google Scholar
  32. Negri M, Salci T, Shinobu-Mesquita C, Capoci I, Svidzinski T, Kioshima E (2014) Early state research on antifungal natural products. Molecules 19(3):2925–2956Google Scholar
  33. Ogawa H, Fujimura M, Takeuchi Y et al (2009) Efficacy of itraconazole in the treatment of patients with chronic cough whose sputa yield basidiomycetous fungi-fungus-associated chronic cough (FACC). J Asthma 46(4):407–412Google Scholar
  34. Oltu I, Rudic V (2016) Antifungal activity of extracts from Arthrospira platensis against some pathogens, causing invasive mycoses. Curierul Med 59(6):9–14Google Scholar
  35. Parks L, Casey W (1996) Fungal sterols. In: Prasad M, Ghannoum M (eds) Lipids of pathogenic fungi. CRC Press, Boca Raton, pp 63–82Google Scholar
  36. Perlin D (2015) Mechanisms of Echinocandin antifungal drug resistance. Ann N Y Acad Sci 1354(1):1–11Google Scholar
  37. Pugazhendhi A, Rathinam MM, Sheela JM (2015) Antifungal activity of cell extract of Spirulina platensis against Aflatoxin producing Aspergillus species. Int J Curr Microbiol App Sci 4(8):1025–1029Google Scholar
  38. Rawat D, Bhargava S (2011) Bioactive compounds from Nostoc species. Curr Res Pharm Sci 02:48–54Google Scholar
  39. Rodríguez-Leguizamón G, Fiori A, Lagrou K et al (2015) New Echinocandin susceptibility patterns for nosocomial Candida albicans in Bogotá, Colombia, in ten tertiary care centres: an observational study. BMC Infect Dis 15(108):1–7Google Scholar
  40. Sanglard D, Coste A, Ferrari S (2009) Antifungal drug resistance mechanisms in fungal pathogens from the perspective of transcriptional gene regulation. FEMS Yeast Res 9(7):1029–1050Google Scholar
  41. Shaieb F, Issa A, Maragaa A (2014) Antimicrobial activity of crude extracts of cyanobacteria Nostoc commune and Spirulina platensis. Arch Biomed Sci 2(2):34–41Google Scholar
  42. Shishido T, Humisto A, Jokela J et al (2015) Antifungal compounds from cyanobacteria. Mar Drugs 13(4):2124–2140Google Scholar
  43. Silva P, Gonçalves S, Santos N (2009) Defensins: antifungal lessons from eukaryotes. Front Microbiol 5:97Google Scholar
  44. Singh PK, Kathuria S, Agarwal K et al (2013) Clinical significance and molecular characterization of nonsporulating molds isolated from the respiratory tracts of bronchopulmonary mycosis patients with special reference to basidiomycetes. J Clin Microbiol 51(10):3331–3337Google Scholar
  45. Subissi A, Monti D, Togni G et al (2010) Ciclopirox: recent nonclinical and clinical data relevant to its use as a topical antimycotic agent. Drugs 70(16):2133–2152Google Scholar
  46. Uniyal V, Bhatt RP, Saxena S et al (2012) Antifungal activity of essential oils and their volatile constituents against respiratory tract pathogens causing Aspergilloma and Aspergillosis by gaseous contact. J Nat Appl Sci 4(1):65–70Google Scholar
  47. Uyisenga J, Nzayino P, Seneza R et al (2010) In vitro study of antibacterial and antifungal activity of Spirulina platensis. Int J Ecol Dev 16(2):10S–15SGoogle Scholar
  48. Velayuthan R, Samudi C, Lakhbeer Singh H, Ng K, Shankar E, Denning D (2018) Estimation of the burden of serious human fungal infections in Malaysia. J Fungi 4(1):38Google Scholar
  49. Vestola J, Shishido TK, Jokela J et al (2014) Hassallidins, antifungal glycolipopeptides, are widespread among cyanobacteria and are the end-product of a nonribosomal pathway. PNAS 111:E1909–E1917Google Scholar
  50. Volk R, Franz H (2006) Antialgal, antibacterial and antifungal activity of two metabolites produced and excreted by cyanobacteria during growth. Microbiol Res 161(2):180–186Google Scholar
  51. Wang J, He W, Huang X et al (2016) Antifungal new Oxepine-containing alkaloids and Xanthones from the Deep-Sea-Derived fungus Aspergillus versicolor SCSIO 05879. J Agric Food Chem 64(14):2910–2916Google Scholar
  52. Zerbo P, Konate K, Ouedraogo M et al (2014) Antioxidant and antifungal profiles of phenol acid rich-fractions from Sida urens l. Against mycelia growth inhibition of some aspergillus and fusarium species. Int J Pharm Pharm Sci 6(1):174–178Google Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Iulian Oltu
    • 1
  • Liliana Cepoi
    • 2
  • Valeriu Rudic
    • 2
  • Ludmila Rudi
    • 2
  • Tatiana Chiriac
    • 2
  • Ana Valuta
    • 2
  • Svetlana Codreanu
    • 2
    Email author
  1. 1.Hospital of Dermatology and Communicable DiseasesChisinauRepublic of Moldova
  2. 2.Institute of Microbiology and BiotechnologyChisinauRepublic of Moldova

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