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Marine Compounds with Anti-Candida sp. Activity: A Promised “Land” for New Antifungals

Anelise Maria Costa Vasconcelos Alves
Natália Cruz-Martins
4,5 and
Célia Fortuna Rodrigues
Institute of Health Sciences, University of International Integration of Afro-Brazilian Lusophony, Av. da Abolição, 3-Centro, Redenção 62790-000, Ceará, Brazil
LEPABE—Laboratory for Process Engineering, Environment, Biotechnology and Energy, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal
ALiCE—Associate Laboratory in Chemical Engineering, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal
TOXRUN—Toxicology Research Unit, Cooperativa de Ensino Superior Politécnico e Universitário—CESPU, 4585-116 Gandra PRD, Portugal
Institute for Research and Innovation in Health (i3S), University of Porto, Rua Alfredo Allen, 4200-135 Porto, Portugal
Author to whom correspondence should be addressed.
J. Fungi 2022, 8(7), 669;
Submission received: 25 May 2022 / Revised: 22 June 2022 / Accepted: 23 June 2022 / Published: 25 June 2022
(This article belongs to the Special Issue Antifungal Drugs 2022)


Candida albicans is still the major yeast causing human fungal infections. Nevertheless, in the last decades, non-Candida albicans Candida species (NCACs) (e.g., Candida glabrata, Candida tropicalis, and Candida parapsilosis) have been increasingly linked to Candida sp. infections, mainly in immunocompromised and hospitalized patients. The escalade of antifungal resistance among Candida sp. demands broadly effective and cost-efficient therapeutic strategies to treat candidiasis. Marine environments have shown to be a rich source of a plethora of natural compounds with substantial antimicrobial bioactivities, even against resistant pathogens, such as Candida sp. This short review intends to briefly summarize the most recent marine compounds that have evidenced anti-Candida sp. activity. Here, we show that the number of compounds discovered in the last years with antifungal activity is growing. These drugs have a good potential to be used for the treatment of candidiasis, but disappointedly the reports have devoted a high focus on C. albicans, neglecting the NCACs, highlighting the need to perform outspreading studies in the near future.

1. Introduction

Candida albicans is the most highly adapted human fungal pathogen causing yeast infections. However, in the last decade, the non-Candida albicans Candida species (NCACs) (e.g., Candida glabrata, Candida krusei, Candida tropicalis, or Candida parapsilosis) have been escalating due to the widespread use and even overuse of broad-spectrum antimicrobial drugs. In addition, and more alarmingly, NCACs have been linked to high rates of antifungal resistance and chronic infections [1,2,3].
Microbial infectious diseases are a serious global health problem. Candidiasis is one of the most predominant fungal infections, particularly in critically ill patients, such as immunosuppressed individuals, under prolonged use of broad-spectrum antibiotics, with HIV, cancer, and even the elderly [4,5,6,7,8]. The growth of antimicrobial resistance (AMR) among both bacteria and fungi is still escalating, and, by 2050, about 10 million people are expected to die per year, and billions will be spent [8,9]. Up-to-date reports indicate that the increase in AMR also involves Candida sp. [2,10,11,12], and mounting evidence has supported the major role of other diseases (e.g., cardiovascular, neurological) in this interplay [13,14]. It is, thus, imperative to slow down the rise of AMR (in Candida sp.), to cut the demand for antifungal drugs, and to increase the supply of new and effective drugs against drug-resistant microorganisms [15]. Henceforward, promoting the investment in alternative antifungal drugs and refining the existing ones is of global urgency to extend the current stock of drugs. In this sense, the search for novel anti-Candida sp. drugs is imperative, particularly from natural compounds, such as those deriving from marine sources.
Oceans and deep seas cover approximately 70% of the Earth and are the habitat of around 80% of all species [16,17], reaching bacteria, fungi, invertebrates, and complex organisms [18]. In the 1950s, Bergmann et al. discovered the first marine compounds with pharmacological importance (antivirals)—spongothymidine and spongouridine—extracted from Tectitethya crypta (Caribbean sponge) [19]. In the last years, the advances in technological approaches (e.g., remotely operated vehicles or closed-circuit computerized mixed gas rebreathers) have made it possible to deeply explore the marine environment in order to search for novel compounds [19,20]. More than 5000 novel natural products have been extracted from marine organisms living in sea environments [21,22]. Conversely, marine compounds are a source of powerful drugs with antifungal (and/or antibiofilm) potential [23,24,25,26,27]. In fact, marine environments are a huge pool of natural compounds with biological importance, besides being safe for human use as antifungals [23,24]. This may be an incomparable chance for the search and formulation of new drugs [23], particularly in human biomedical applications [28]. Marine biopolymers are also presently an active research area towards a deeper knowledge of effective drug delivery systems and to develop novel therapies. These compounds are highly interesting as biomaterials for clinical applications due to their abundance, biocompatibility, biodegradability, ease of surface modification, inexpensiveness, stability, and non-toxic nature [24].
In this sense, this brief review recapitulates the marine compounds that have been recently studied owing to their anti-Candida effects. The search was performed using the NBCI platform (PubMed), using the keywords “anti-candida”, ”marine”, ”drugs”, and selecting the years 2017 to 2022.

2. Marine Compounds, Potential Antimicrobial Activity, and Current Drug Marine Biotech

Natural compounds are one of the best alternative resources to explore bioactive drug candidates. Undeniably, these compounds have properties that have proved to be beneficial for the management of candidiasis, also eliminating and/or out-competing with the involved microorganisms. In addition, they have been explored in biotech research and industry, proving to be interesting alternatives to the currently available biopolymers. The next sections will discuss these points.

Marine Compounds with Anti-Candida sp. Effects

There is an array of marine compounds that have been identified as having antimicrobial activity. Recently, the isolation of certain components of mollusks’ defense systems has been studied. Hong Kong oysters (Crassostrea hongkongensis) infected by Vibrio parahaemolyticus produce peptides with potent antibacterial and antifungal activity, showing biological activity against C. albicans, and without cytotoxicity in vitro and in rodents [29]. Turbinmicin, a compound from a sea squirt microbiome constituent, Micromonospora sp., has evidenced to be a potent antifungal activity in vitro and in vivo against Candida auris. In addition, it was shown to be a safe drug, targeting the Sec14 of the vesicular trafficking pathway [30]. Similarly, the American oyster (Crassostrea virginica) showed to produce a defensive compound exhibiting strong antimicrobial activity. Seo and colleagues [31] designed peptides arginine-rich analogs into antibiotic candidates (A0, A1, A2, A3, and A4), the last two showed action against C. albicans growth without displaying cell toxicity [31]. More complex organism extracts, such as the Fish Skin Mucous (FSM) derived from Dasyatis pastinaca, have also shown significant and species-specific activity against strains of Candida sp. It is thought that these results may be linked to a chitinase expression, which targets chitin, a structural polysaccharide found in large proportions in the fungal wall [32]. The Q-Griffithsin (Q-GRFT), a derivation of a marine red algal lectin, also binds to the cell wall and exhibits activity against strains of Candida sp. Its mechanism of action is through to be related to the induction of cell death by disruption of cell wall integrity after binding to α-mannan, and the trigger of reactive oxidative species (ROS) formation. Moreover, the Q-GRFT inhibits the growth of C. glabrata, C. parapsilosis, and C. krusei and C. auris [33].
However, not only does red algae exert anti-Candida effects, but the crude extracts of seaweeds also obtained from the Riacho Doce beach, Alagoas (Brazil), present minimum inhibitory concentrations (MIC), ranging from 0.03 to 16.00 μg/mL against Trichophyton rubrum, Trichophyton tonsurans, Trichophyton mentagrophytes, Microsporum canis, Microsporum gypseum, and yeasts C. albicans, C. krusei, Candida guilliermondi, and C. parapsilosis, respectively. When the extraction methods were compared, the dichloromethane, methanol, and ethanol extracts showed the largest inhibition abilities against C. albicans growth [34]. Peptides and proteins that have shown anti-Candida properties are summarized in Table 1.
Additionally, from several sponge species, a large arsenal of other molecules can be isolated: nucleosides, terpenes, sterols, cyclic peptides, and alkaloids (Table 2), presenting huge pharmacological importance. The EtOH extract of Oceanapia sp., a marine sponge, contains Oceanalin B, a sphingoid tetrahydoisoquinoline β-glycosides, with remarkable in vitro activity against C. glabrata [37]. In addition to molecules produced directly by sponges, it is possible to obtain products from microorganisms living in symbiosis with them. The symbiotic organisms are bacteria, archaea, microalgae, and fungi, totaling a volume of 40% of the sponge’s body. These microorganism communities hosted in sponges produce bioactive secondary metabolites with antimicrobial effects. Recently, culturing fungi under different conditions has resulted in the production of new secondary metabolites that are not observed previously in regular culture protocols. Two dimeric antifungal alkaloids, entitled fusarypyridines A and B, were isolated from the organic extract of the fungus Fusarium sp. LY019 living in symbiosis with the sponge Suberea mollis in the Red Sea. These compounds showed selective and potent effects against C. albicans (MIC values of 8.0 and 8.0 µM, respectively) [38]. Evidence suggests the alkaloid derivatives 6a and 6b antifungal have activity against C. albicans, C. glabrata, C. tropicalis, and C. krusei. A synergistic in vitro effect was observed with ketoconazole by binding to membrane ergosterol and, consequently, triggering the lysis of fungal cells [39]. Similarly, the sponge Callyspongia siphonella hosts the actinomycete strain Streptomyces coelicolor LY001. The extract obtained from this strain was purified and gave rise to chlorinated derivatives of 3-phenylpropanoic acid (n = 3) that demonstrated significant and selective activities against C. albicans [40]. In another study, new non-brominated pyrrole-2-carboxamide alkaloids, nakamurins A–C (1–3) were obtained from the sponge Agelas nakamurai (Xisha Islands, South China Sea). Compound 2 was identified as an antimicrobial with weak activity against C. albicans (MIC = 60 mg/mL) and no toxic effect in vitro [41]. In addition, Hemimycale sp., a species endemic to the Red Sea, produces C–E hemimycalins (secondary metabolites) that inhibit the growth of bacteria and fungi such as Escherichia coli and C. albicans [42].
Other marine chemical compounds have shown effective antifungal effects (Table 3, Table 4 and Table 5. Oceanapiside (OPS), a sphingolipid, presents a fungicidal effect against fluconazole-resistant C. glabrata. Probably, the inhibition of polarized growth promoted by OPS is due to the disruption of organized actin. Phytosphingosine (PHS) was able to reverse OPS activity which indicates that it blocks fungal sphingolipid metabolism by specifically inhibiting the conversion step of PHS to phytoceramide [58]. Similarly, marine polyunsaturated fatty acids inhibit biofilm formation of C. albicans and Candida dubliniensis. Mitochondrial metabolism and biofilm biomass are affected by these fatty acids, as well as the cell wall morphology [59].
The Antarctic emperor penguin (Aptenodytes forsteri) also hosts bacteria that produce antimicrobial secondary metabolites. For example, the NJES-13T, an actinobacterial strain present in its gut microbiota, is a producer of anguciclinone, gepyromycin (GPM), and 2-hydroxy-tetrangomycin (2-HT), as well as complex bioflocculation active exopolysaccharide (EPS) metabolites. It was observed the angucycline/angucyclinone derivative metabolites have been isolated from this strain with inhibitory activity against the microorganisms Staphylococcus aureus, Bacillus subtilis, and C. albicans [44]. Similarly, some strains of Aspergillus sp. are antimicrobial producers. Among the antimicrobial compounds from Aspergillus species are observed xanthones, alkaloids, cyclic peptides, and terpenes. Wu et al. (2020) studied the extract of Aspergillus terreus RA2905 hosted in the sea hare Aplysia pulmonica. In this extract, they isolated two new thiodiketopiperazines, emestrins L and M, five analogs (3–7), and five dihydroisocoumarins (8–12). Among the isolated compounds, only the number 3 presented activity against C. albicans ATCC10231 (MIC 32 μg/mL) [57]. However, eight compounds isolated from an Aspergillus fumigatus D strain, living in symbiosis with the species Edgeworthia chrysantha Lindl, showed no significant effect on C. albicans. The Penicillium genus may also produce bioactive compounds as immunosuppressants, harmful mycotoxins, antibacterial and antifungal. The extract of Penicillium sp. SY2107 from Mariana Trench sediment prepared in a rice medium inhibits microbial growth [46]. In addition, another team characterized the antimicrobial activity of organic extracts of fungi belonging to the genera Penicillium, Cladosporium, Emericellopsis, and Plectosphaerella. The study observed 49 mycotoxins and functional metabolites, indicating a great chemical diversity. The highest number of compounds was isolated from fungi of the genus Penicillium, on average 165 parent ions per strain. Regarding bioactivity, Penicillium sp. 31.68F1B was the strain with the most expressive results. This fungus showed activity against seven plant and human pathogens, and C. albicans was the microorganism most sensitive to the compounds of this strain [47]. Likewise, eutypellenoid B, isolated from the extract of Eutypella sp. D-1 inhibits fungi growth of the following species C. parapsilosis (MIC= 8 μg/mL), C. albicans (MIC= 8 μg/mL), C. glabrata (MIC =16 μg/mL), and C. tropicalis (MIC= 32 μg/mL) [48].
Marine bacteria are also targets for pharmacotherapeutic studies. For example, new compounds belonging to the alkaloid class were recently isolated from an Acinetobacter sp. ZZ1275 strain. These compounds are Indolepyrazines A and B, and they showed antimicrobial activities against methicillin-resistant S. aureus, E. coli, and C. albicans with MIC values of 12 μg/mL, 8–10 μg/mL, and 12–14 μg/mL, respectively [45]. Another interesting finding is the synthetic molecules based on natural compounds, such as the N-methylated analog proline-rich tetracyclopeptide that presented efficient antifungal effects against C. albicans [35]. The Candida sp. biofilms treated with purified marine bacterial DNase (MBD) from a strain of Vibrio alginolyticus (AMSII) were also capable of decreasing 60–80% biomass and significantly reducing the rate of biofilms formation on urinary catheters while disrupts yeast to dimorphic hyphae switch in C. albicans [36].
On the other hand, some compounds from marine-derived microorganisms have also shown to be inefficient as antifungals. The calcomycins isolated from the in vitro culture of a strain of Streptomyces sp. HK-2006-1 shows selective activity against only bacteria such as S. aureus while not affecting the growth of fungi such as C. albicans and Aspergillus niger [56]. These and other works that have studied specific marine compounds for anti-Candida sp. activity are summarized in Table 1, Table 2, Table 3, Table 4 and Table 5.

3. Final Remarks

AMR has hugely complicated the treatment of infections while facilitating the progression to chronic or recurrent stages, and thus new antimicrobial drugs are urgently necessary for effective antibiotic therapy. Specifically, the search for new antimicrobials within the species that inhabit the oceans seems promissory, leading to the identification of a series of novel compounds with a great ability to manage fungal infections, including candidiasis.
Marine environments are an almost inexhaustible source of resources of varied natural compounds, with substantial antimicrobial bioactivities, even against resistant pathogens [71]. Among the marine taxa, bacteria, fungi themselves, sponges, and soft corals, have shown to be a rich source (but not only) of novel biologically active drugs. In addition, the use of marine animals and microorganisms has the advantage of having low associated costs and a great yield to produce anti-Candida sp. drugs. Regrettably, we noticed a strong gap within the Candida sp. that have been tested in the published reports. In fact, almost only exclusively C. albicans has been the target of an intense study, setting aside, in almost all studies, the NCACs. Considering that these Candida sp. are emerging as strong human pathogens in the last decades and have been linked to high rates of antifungal resistance (such as C. glabrata and Candida auris) [72], it is, thus, of utmost interest to extend these studies to the remaining (fungal) species.

Author Contributions

Conceptualization, C.F.R.; methodology, A.M.C.V.A., N.C.-M. and C.F.R.; validation, C.F.R.; investigation, A.M.C.V.A., N.C.-M. and C.F.R.; writing—original draft preparation, A.M.C.V.A., N.C.-M. and C.F.R.; writing—review and editing, N.C.-M. and C.F.R.; supervision, C.F.R. All authors have read and agreed to the published version of the manuscript.


This work received no funding support.

Conflicts of Interest

The authors declare no conflict of interest.


  1. Cannon, R.D. Oral Fungal Infections: Past, Present, and Future. Front. Oral Health 2022, 3, 838639. [Google Scholar] [CrossRef] [PubMed]
  2. Andrade, J.C.; Kumar, S.; Kumar, A.; Černáková, L.; Rodrigues, C.F. Application of Probiotics in Candidiasis Management. Crit. Rev. Food Sci. Nutr. 2021, 1–16. [Google Scholar] [CrossRef] [PubMed]
  3. Corzo-León, D.E.; Munro, C.A.; MacCallum, D.M. An Ex Vivo Human Skin Model to Study Superficial Fungal Infections. Front. Microbiol. 2019, 10, 1172. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  4. Khosravi, A.R.; Mansouri, P.; Saffarian, Z.; Vahedi, G.; Nikaein, D. Chronic Mucocutaneous Candidiasis, a Case Study and Literature Review. J. Mycol. Med. 2018, 28, 206–210. [Google Scholar] [CrossRef] [PubMed]
  5. Vos, T.; Abajobir, A.A.; Abate, K.H.; Abbafati, C.; Abbas, K.M.; Abd-Allah, F.; Abdulkader, R.S.; Abdulle, A.M.; Abebo, T.A.; Abera, S.F.; et al. Global, Regional, and National Incidence, Prevalence, and Years Lived with Disability for 328 Diseases and Injuries for 195 Countries, 1990–2016: A Systematic Analysis for the Global Burden of Disease Study 2016. Lancet 2017, 390, 1211–1259. [Google Scholar] [CrossRef] [Green Version]
  6. Oral Health Achieving Better Oral Health as Part of the Universal Health Coverage and Noncommunicable Disease Agendas towards 2030. Available online: (accessed on 23 December 2020).
  7. Bongomin, F.; Gago, S.; Oladele, R.; Denning, D. Global and Multi-National Prevalence of Fungal Diseases—Estimate Precision. J. Fungi 2017, 3, 57. [Google Scholar] [CrossRef]
  8. Ten Threats to Global Health in 2019. Available online: (accessed on 6 January 2020).
  9. WHO Antimicrobial Resistance. Global Report on Surveillance. World Health Organ. 2014, 61, 12–28. [Google Scholar] [CrossRef]
  10. Panariello, B.H.D.; de Araújo Costa, C.A.G.; Pavarina, A.C.; Santiago, S.L.; Duarte, S. Advances and Challenges in Oral Biofilm Control. Curr. Oral Health Rep. 2017, 4, 29–33. [Google Scholar] [CrossRef]
  11. Rodrigues, C.F.; Henriques, M. Liposomal and Deoxycholate Amphotericin B Formulations: Effectiveness against Biofilm Infections of Candida spp. Pathogens 2017, 6, 62. [Google Scholar] [CrossRef] [Green Version]
  12. BDJ Team. Antibiotic Resistance among Patients with Severe Gum Disease Is Increasing. Nat. Publ. Group 2018, 5, 18117. [Google Scholar] [CrossRef]
  13. Rautemaa, R.; Lauhio, A.; Cullinan, M.P.; Seymour, G.J. Oral Infections and Systemic Disease—An Emerging Problem in Medicine. Clin. Microbiol. Infect. 2007, 13, 1041–1047. [Google Scholar] [CrossRef] [PubMed]
  14. Bui, F.Q.; Almeida-da-Silva, C.L.C.; Huynh, B.; Trinh, A.; Liu, J.; Woodward, J.; Asadi, H.; Ojcius, D.M. Association between Periodontal Pathogens and Systemic Disease. Biomed. J. 2019, 42, 27–35. [Google Scholar] [CrossRef] [PubMed]
  15. CDC. 2019 Antibiotic Resistance Threats Report. Available online: (accessed on 22 February 2022).
  16. Sutton, T.T.; Clark, M.R.; Dunn, D.C.; Halpin, P.N.; Rogers, A.D.; Guinotte, J.; Bograd, S.J.; Angel, M.V.; Perez, J.A.A.; Wishner, K.; et al. A Global Biogeographic Classification of the Mesopelagic Zone. Deep Sea Res. Part I Oceanogr. Res. Pap. 2017, 126, 85–102. [Google Scholar] [CrossRef]
  17. Barzkar, N.; Jahromi, S.T.; Poorsaheli, H.B.; Vianello, F. Metabolites from Marine Microorganisms, Micro, and Macroalgae: Immense Scope for Pharmacology. Mar. Drugs 2019, 17, 464. [Google Scholar] [CrossRef] [Green Version]
  18. Ebada, S.S.; Proksch, P. The Chemistry of Marine Sponges. Handb. Mar. Nat. Prod. 2012, 191–293. [Google Scholar] [CrossRef]
  19. Petersen, L.E.; Kellermann, M.Y.; Schupp, P. Secondary Metabolites of Marine Microbes: From Natural Products Chemistry to Chemical Ecology. YOUMARES 2020, 9, 159–180. [Google Scholar] [CrossRef] [Green Version]
  20. Carte, B.K. Marine Natural Products as a Source of Novel Pharmacological Agents. Curr. Opin. Biotechnol. 1993, 4, 275–279. [Google Scholar] [CrossRef]
  21. Senthilkumar, K.; Kim, S.K. Marine Invertebrate Natural Products for Anti-Inflammatory and Chronic Diseases. Evid. Based Complementary Altern. Med. 2013, 2013, 572859. [Google Scholar] [CrossRef]
  22. Jha, R.K.; Zi-Rong, X. Biomedical Compounds from Marine Organisms. Mar. Drugs 2004, 2, 123–146. [Google Scholar] [CrossRef] [Green Version]
  23. Kim, S.K.; Bhatnagar, I.; Kang, K.H. Development of Marine Probiotics. Prospects and Approach. In Advances in Food and Nutrition Research; Academic Press Inc.: Cambridge, MA, USA, 2012; Volume 65, pp. 353–362. [Google Scholar]
  24. Manivasagan, P.; Bharathiraja, S.; Moorthy, M.S.; Oh, Y.O.; Seo, H.; Oh, J. Marine Biopolymer-Based Nanomaterials as a Novel Platform for Theranostic Applications. Polym. Rev. 2017, 57, 631–667. [Google Scholar] [CrossRef]
  25. Wu, Q.; Patočka, J.; Kuča, K. Insect Antimicrobial Peptides, a Mini Review. Toxins 2018, 10, 461. [Google Scholar] [CrossRef] [PubMed]
  26. Yi, H.Y.; Chowdhury, M.; Huang, Y.D.; Yu, X.Q. Insect Antimicrobial Peptides and Their Applications. Appl. Microbiol. Biotechnol. 2014, 98, 5807–5822. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  27. Zhang, Y.; Wang, X.; Li, H.; Ni, C.; Du, Z.; Yan, F. Human Oral Microbiota and Its Modulation for Oral Health. Biomed. Pharmacother. 2018, 99, 883–893. [Google Scholar] [CrossRef] [PubMed]
  28. Shin, S.; Ikram, M.; Subhan, F.; Kang, H.Y.; Lim, Y.; Lee, R.; Jin, S.; Jeong, Y.H.; Kwak, J.Y.; Na, Y.J.; et al. Alginate-Marine Collagen-Agarose Composite Hydrogels as Matrices for Biomimetic 3D Cell Spheroid Formation. RSC Adv. 2016, 6, 46952–46965. [Google Scholar] [CrossRef]
  29. Mao, F.; Bao, Y.; Wong, N.K.; Huang, M.; Liu, K.; Zhang, X.; Yang, Z.; Yi, W.; Shu, X.; Xiang, Z.; et al. Large-Scale Plasma Peptidomic Profiling Reveals a Novel, Nontoxic, Crassostrea hongkongensis-Derived Antimicrobial Peptide against Foodborne Pathogens. Mar. Drugs 2021, 19, 420. [Google Scholar] [CrossRef]
  30. Zhang, F.; Zhao, M.; Braun, D.R.; Ericksen, S.S.; Piotrowski, J.S.; Nelson, J.; Peng, J.; Ananiev, G.E.; Chanana, S.; Barns, K.; et al. A Marine Microbiome Antifungal Targets Urgent-Threat Drug-Resistant Fungi. Science 2020, 370, 974–978. [Google Scholar] [CrossRef]
  31. Seo, J.K.; Kim, D.G.; Lee, J.E.; Park, K.S.; Lee, I.A.; Lee, K.Y.; Kim, Y.O.; Nam, B.H. Antimicrobial Activity and Action Mechanisms of Arg-Rich Short Analog Peptides Designed from the c-Terminal Loop Region of American Oyster Defensin (Aod). Mar. Drugs 2021, 19, 451. [Google Scholar] [CrossRef]
  32. Fuochi, V.; Li Volti, G.; Camiolo, G.; Tiralongo, F.; Giallongo, C.; Distefano, A.; Petronio, G.P.; Barbagallo, I.; Viola, M.; Furneri, P.M.; et al. Antimicrobial and Anti-Proliferative Effects of Skin Mucus Derived from Dasyatis pastinaca (Linnaeus, 1758). Mar. Drugs 2017, 15, 342. [Google Scholar] [CrossRef] [Green Version]
  33. Nabeta, H.W.; Kouokam, J.C.; Lasnik, A.B.; Fuqua, J.L.; Palmer, K.E. Novel Antifungal Activity of Q-Griffithsin, a Broad-Spectrum Antiviral Lectin. Microbiol. Spectr. 2021, 9, e00957-21. [Google Scholar] [CrossRef]
  34. Guedes, E.A.C.; dos Santos Araújo, M.A.; Souza, A.K.P.; de Souza, L.I.O.; de Barros, L.D.; de Albuquerque Maranhão, F.C.; Sant’Ana, A.E.G. Antifungal Activities of Different Extracts of Marine Macroalgae Against Dermatophytes and Candida Species. Mycopathologia 2012, 174, 223–232. [Google Scholar] [CrossRef]
  35. Dahiya, R.; Kumar, S.; Khokra, S.L.; Gupta, S.V.; Sutariya, V.B.; Bhatia, D.; Sharma, A.; Singh, S.; Maharaj, S. Toward the Synthesis and Improved Biopotential of an N-Methylated Analog of a Proline-Rich Cyclic Tetrapeptide from Marine Bacteria. Mar. Drugs 2018, 16, 305. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  36. Farisa Banu, S.; Thamotharan, S.; Gowrishankar, S.; Karutha Pandian, S.; Nithyanand, P. Marine Bacterial DNase Curtails Virulence and Disrupts Biofilms of Candida Albicans and Non-Albicans Candida Species. Biofouling 2019, 35, 975–985. [Google Scholar] [CrossRef] [PubMed]
  37. Makarieva, T.N.; Ivanchina, N.V.; Dmitrenok, P.S.; Guzii, A.G.; Stonik, V.A.; Dalisay, D.S.; Molinski, T.F. Oceanalin B, a Hybrid α,ω-Bifunctionalized Sphingoid Tetrahydroisoquinoline β-Glycoside from the Marine Sponge Oceanapia sp. Mar. Drugs 2021, 19, 635. [Google Scholar] [CrossRef] [PubMed]
  38. Shaala, L.A.; Alzughaibi, T.; Genta-Jouve, G.; Youssef, D.T.A. Fusaripyridines A and B; Highly Oxygenated Antimicrobial Alkaloid Dimers Featuring an Unprecedented 1,4-Bis(2-Hydroxy-1,2-Dihydropyridin-2-Yl)Butane-2,3-Dione Core from the Marine Fungus Fusarium Sp. LY019. Mar. Drugs 2021, 19, 505. [Google Scholar] [CrossRef] [PubMed]
  39. Andrade, J.T.; Lima, W.G.; Sousa, J.F.; Saldanha, A.A.; De Sá, N.P.; Morais, F.B.; Prates Silva, M.K.; Ribeiro Viana, G.H.; Johann, S.; Soares, A.C.; et al. Design, Synthesis, and Biodistribution Studies of New Analogues of Marine Alkaloids: Potent In Vitro and In Vivo Fungicidal Agents against Candida spp. Eur. J. Med. Chem. 2021, 210, 113048. [Google Scholar] [CrossRef]
  40. Shaala, L.A.; Youssef, D.T.A.; Alzughaibi, T.A.; Elhady, S.S. Antimicrobial Chlorinated 3-Phenylpropanoic Acid Derivatives from the Red Sea Marine Actinomycete Streptomyces Coelicolor LY001. Mar. Drugs 2020, 18, 450. [Google Scholar] [CrossRef]
  41. Chu, M.-J.; Tang, X.-L.; Qin, G.-F.; Sun, Y.-T.; Li, L.; de Voogd, N.J.; Li, P.-L.; Li, G.-Q. Pyrrole Derivatives and Diterpene Alkaloids from the South China Sea Sponge Agelas Nakamurai. Chem. Biodivers. 2017, 14, e1600446. [Google Scholar] [CrossRef]
  42. Shaala, L.A.; Youssef, D.T.A. Hemimycalins c–e; Cytotoxic and Antimicrobial Alkaloids with Hydantoin and 2-Iminoimidazolidin-4-One Backbones from the Red Sea Marine Sponge Hemimycale sp. Mar. Drugs 2021, 19, 691. [Google Scholar] [CrossRef]
  43. Wu, J.S.; Shi, X.H.; Zhang, Y.H.; Shao, C.L.; Fu, X.M.; Li, X.; Yao, G.S.; Wang, C.Y. Benzyl Furanones and Pyrones from the Marine-Derived Fungus Aspergillus Terreus Induced by Chemical Epigenetic Modification. Molecules 2020, 25, 3927. [Google Scholar] [CrossRef]
  44. Zhu, W.Z.; Wang, S.H.; Gao, H.M.; Ge, Y.M.; Dai, J.; Zhang, X.L.; Yang, Q. Characterization of Bioactivities and Biosynthesis of Angucycline/Angucyclinone Derivatives Derived from Gephyromycinifex aptenodytis Gen. Nov., Sp. Nov. Mar. Drugs 2022, 20, 34. [Google Scholar] [CrossRef]
  45. Anjum, K.; Kaleem, S.; Yi, W.; Zheng, G.; Lian, X.; Zhang, Z. Novel Antimicrobial Indolepyrazines A and B from the Marine-Associated Acinetobacter Sp. ZZ1275. Mar. Drugs 2019, 17, 89. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  46. Kaleem, S.; Qin, L.; Yi, W.; Lian, X.Y.; Zhang, Z. Bioactive Metabolites from the Mariana Trench Sedi-ment-Derived Fungus Penicillium sp. SY2107. Mar. Drugs 2020, 18, 258. [Google Scholar] [CrossRef] [PubMed]
  47. Oppong-Danquah, E.; Passaretti, C.; Chianese, O.; Blümel, M.; Tasdemir, D. Mining the Metabolome and the Agricultural and Pharmaceutical Potential of Sea Foam-Derived Fungi. Mar. Drugs 2020, 18, 128. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  48. Yu, H.B.; Wang, X.L.; Xu, W.H.; Zhang, Y.X.; Qian, Y.S.; Zhang, J.P.; Lu, X.L.; Liu, X.Y. Eutypellenoids a–C, New Pimarane Diterpenes from the Arctic Fungus Eutypella sp. D-1. Mar. Drugs 2018, 16, 284. [Google Scholar] [CrossRef] [Green Version]
  49. Zhang, K.; Zhang, X.; Lin, R.; Yang, H.; Song, F.; Xu, X.; Wang, L. New Secondary Metabolites from the Marine-Derived Fungus Talaromyces Mangshanicus BTBU20211089. Mar. Drugs 2022, 20, 79. [Google Scholar] [CrossRef]
  50. Hua, Y.; Pan, R.; Bai, X.; Wei, B.; Chen, J.; Wang, H.; Zhang, H. Aromatic Polyketides from a Symbiotic Strain Aspergillus Fumigatus D and Characterization of Their Biosynthetic Gene D8.T287. Mar. Drugs 2020, 18, 324. [Google Scholar] [CrossRef]
  51. Yang, W.C.; Bao, H.Y.; Liu, Y.Y.; Nie, Y.Y.; Yang, J.M.; Hong, P.Z.; Zhang, Y. Depsidone Derivatives and a Cyclopeptide Produced by Marine Fungus Aspergillus Unguis under Chemical Induction and by Its Plasma Induced Mutant. Molecules 2018, 23, 2245. [Google Scholar] [CrossRef] [Green Version]
  52. Subko, K.; Kildgaard, S.; Vicente, F.; Reyes, F.; Genilloud, O.; Larsen, T.O. Bioactive Ascochlorin Analogues from the Marine-Derived Fungus Stilbella Fimetaria. Mar. Drugs 2021, 19, 46. [Google Scholar] [CrossRef]
  53. Xu, X.; Li, J.; Zhang, K.; Wei, S.; Lin, R.; Polyak, S.W.; Yang, N.; Song, F. New Isocoumarin Analogues from the Marine-Derived Fungus Paraphoma Sp. CUGBMF180003. Mar. Drugs 2021, 19, 313. [Google Scholar] [CrossRef]
  54. Hu, J.; Li, Z.; Gao, J.; He, H.; Dai, H.; Xia, X.; Liu, C.; Zhang, L.; Song, F. New Diketopiperazines from a Marine-Derived Fungus Strain Aspergillus Versicolor MF180151. Mar. Drugs 2019, 17, 262. [Google Scholar] [CrossRef] [Green Version]
  55. Xu, X.; Han, J.; Lin, R.; Polyak, S.W.; Song, F. Two New Piperazine-Triones from a Marine-Derived Strep-tomycetes Sp. Strain SMS636. Mar. Drugs 2019, 17, 186. [Google Scholar] [CrossRef] [Green Version]
  56. Jiang, S.; Zhang, L.; Pei, X.; Deng, F.; Hu, D.; Chen, G.; Wang, C.; Hong, K.; Yao, X.; Gao, A.H. Chalcomycins from Marine-Derived Streptomyces sp. and Their Antimicrobial Activities. Mar. Drugs 2017, 15, 153. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  57. Wu, J.-S.; Shi, X.-H.; Yao, G.-S.; Shao, C.-L.; Fu, X.-M.; Zhang, X.-L.; Guan, H.-S.; Wang, C.-Y. New Thi-odiketopiperazine and 3,4-Dihydroisocoumarin Derivatives from the Marine-Derived Fungus Aspergillus terreus. Mar. Drugs 2020, 18, 132. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  58. Dalisay, D.S.; Rogers, E.W.; Molinski, T.F. Oceanapiside, a Marine Natural Product, Targets the Sphingolipid Pathway of Fluconazole-Resistant Candida Glabrata. Mar. Drugs 2021, 19, 126. [Google Scholar] [CrossRef] [PubMed]
  59. Thibane, V.S.; Kock, J.L.F.; Ells, R.; van Wyk, P.W.J.; Pohl, C.H. Effect of Marine Polyunsaturated Fatty Acids on Biofilm Formation of Candida Albicans and Candida Dubliniensis. Mar. Drugs 2010, 8, 2597–2604. [Google Scholar] [CrossRef]
  60. Esquivel-Hernández, D.A.; Rodríguez-Rodríguez, J.; Cuéllar-Bermúdez, S.P.; García-Pérez, J.S.; Mancera-Andrade, E.I.; Núñez-Echevarría, J.E.; Ontiveros-Valencia, A.; Rostro-Alanis, M.; García-García, R.M.; Torres, J.A.; et al. Effect of Supercritical Carbon Dioxide Extraction Parameters on the Biological Activities and Metabolites Present in Extracts from Arthrospira platensis. Mar. Drugs 2017, 15, 174. [Google Scholar] [CrossRef] [Green Version]
  61. Blessie, E.J.; Wruck, W.; Abbey, B.A.; Ncube, A.; Graffmann, N.; Amarh, V.; Arthur, P.K.; Adjaye, J. Tran-scriptomic Analysis of Marine Endophytic Fungi Extract Identifies Highly Enriched Anti-Fungal Fractions Targeting Cancer Pathways in HepG2 Cell Lines. BMC Genomics 2020, 21, 265. [Google Scholar] [CrossRef]
  62. Kvetkina, A.; Kostina, E.; Gladkikh, I.; Chausova, V.; Yurchenko, E.; Bakunina, I.; Pivkin, M.; Anastyuk, S.; Popov, R.; Monastyrnaya, M.; et al. Deep-Sea Anemones Are Prospective Source of New Antimicrobial and Cytotoxic Compounds. Mar. Drugs 2021, 19, 654. [Google Scholar] [CrossRef]
  63. Costa, B.; Mota, R.; Tamagnini, P.; Martins, C.M.L.; Costa, F. Natural Cyanobacterial Polymer-Based Coating as a Preventive Strategy to Avoid Catheter-Associated Urinary Tract Infections. Mar. Drugs 2020, 18, 279. [Google Scholar] [CrossRef]
  64. Galdiero, E.; Ricciardelli, A.; D’Angelo, C.; de Alteriis, E.; Maione, A.; Albarano, L.; Casillo, A.; Corsaro, M.M.; Tutino, M.L.; Parrilli, E. Pentadecanoic Acid against Candida Albicans-Klebsiella Pneumoniae Biofilm: Towards the Development of an Anti-Biofilm Coating to Prevent Polymicrobial Infections. Res. Microbiol. 2021, 172, 103880. [Google Scholar] [CrossRef]
  65. Leutou, A.S.; McCall, J.R.; York, R.; Govindapur, R.R.; Bourdelais, A.J. Anti-Inflammatory Activity of Gly-colipids and a Polyunsaturated Fatty Acid Methyl Ester Isolated from the Marine Dinoflagellate Karenia Mikimotoi. Mar. Drugs 2020, 18, 138. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  66. Pham, G.N.; Kang, D.Y.; Kim, M.J.; Han, S.J.; Lee, J.H.; Na, M. Isolation of Sesquiterpenoids and Steroids from the Soft Coral Sinularia Brassica and Determination of Their Absolute Configuration. Mar. Drugs 2021, 19, 523. [Google Scholar] [CrossRef] [PubMed]
  67. Jamison, M.T.; Wang, X.; Cheng, T.; Molinski, T.F. Synergistic Anti-Candida Activity of Bengazole A in the Presence of Bengamide A. Mar. Drugs 2019, 17, 102. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  68. Gargouch, N.; Elleuch, F.; Karkouch, I.; Tabbene, O.; Pichon, C.; Gardarin, C.; Rihouey, C.; Picton, L.; Ab-delkafi, S.; Fendri, I.; et al. Potential of Exopolysaccharide from Porphyridium Marinum to Contend with Bacterial Proliferation, Biofilm Formation, and Breast Cancer. Mar. Drugs 2021, 19, 66. [Google Scholar] [CrossRef] [PubMed]
  69. Chen, X.; Li, H.; Qiao, X.; Jiang, T.; Fu, X.; He, Y.; Zhao, X. Agarose Oligosaccharide- Silver Nanoparticle- Antimicrobial Peptide- Composite for Wound Dressing. Carbohydr. Polym. 2021, 269, 118258. [Google Scholar] [CrossRef] [PubMed]
  70. Zhang, M.; Qiao, X.; Han, W.; Jiang, T.; Liu, F.; Zhao, X. Alginate-Chitosan Oligosaccharide-ZnO Composite Hydrogel for Accelerating Wound Healing. Carbohydr. Polym. 2021, 266, 118100. [Google Scholar] [CrossRef]
  71. Abdelmohsen, U.R.; Balasubramanian, S.; Oelschlaeger, T.A.; Grkovic, T.; Pham, N.B.; Quinn, R.J.; Hentschel, U. Potential of Marine Natural Products against Drug-Resistant Fungal, Viral, and Parasitic Infections. Lancet Infect Dis. 2017, 17, e30–e41. [Google Scholar] [CrossRef]
  72. Černáková, L.; Roudbary, M.; Brás, S.; Tafaj, S.; Rodrigues, C.F. Candida Auris: A Quick Review on Identi-fication, Current Treatments, and Challenges. Int. J. Mol. Sci. 2021, 22, 4470. [Google Scholar] [CrossRef]
Table 1. Antifungal activity of marine peptides and proteins.
Table 1. Antifungal activity of marine peptides and proteins.
CompoundOriginCandida sp.Reference
Up-regulated peptides (URPs) from Oyster plasmaOyster (Crassostrea hongkongensis)
infected by V. parahaemolyticus
Candida albicans[29]
American oyster defensin (AOD)- arginine-rich analogs (A3 and A4)Oyster Crassostrea virginicaCandida albicans[31]
N-methylated proline-rich tetrapeptidesPseudomonas sp. and Pseudoalteromonas sp.Candida albicans[35]
Peptide URP20Crassostrea hongkongensisCandida albicans[29]
Marine bacterial DNase (MBD)Vibrio alginolyticusCandida albicans[36]
Q-Griffithsin (Q-GRFT)Marine red algaeCandida albicans, Candida glabrata, Candida parapsilosis, Candida krusei, Candida auris[33]
Table 2. Antifungal activity of marine alkaloids and esters.
Table 2. Antifungal activity of marine alkaloids and esters.
CompoundOriginCandida sp.Reference
Emethacin CAspergillus terreus RA2905Candida albicans[43]
C-2 hydroxyl substitutes; 2-hydroxy-tetrangomycin;
Strain NJES-13TCandida albicans[44]
Indolepyrazines A and BAcinetobacter sp. ZZ1275Candida albicans[45]
Andrastones B and CPenicillium sp. SY2107Candida albicans[46]
Fusaripyridines A and BFusarium sp. LY019Candida albicans[38]
31.68F1BPenicillium sp.Candida albicans[47]
Diketopiperazine alkaloids cyclo(l-Phe-trans-4-OH-l-Pro) and Cyclo(l-Phe-cis-4-OH-d-Pro)Streptomyces coelicolor LY001 from the sponge Callyspongia siphonellaCandida albicans[40]
Eutypellenoid BEutypella sp. D-1Candida parapsilosis, Candida albicans, Candida glabrata, Candida tropicalis[48]
Talaromanloid A, Talaromydene, 10-hydroxy-8-demethyltalaromydine, 11-hydroxy-8-demethyltalaromydine, talaromylectone, and ditalaromylectones A and BTalaromyces mangshanicus BTBU20211089Candida albicans[49]
Rubrofusarin B, Alternariol 9-O-methyl ether, Fonsecinone D, Asperpyrone A, Asperpyrone D, Fonsecinone B, Fonsecinone A, and Aurasperone AAspergillus fumigatus DCandida albicans[50]
Asperpyranone A and B
Aspergillus terreus RA2905Candida albicans[43]
Aspergillusidone G;
Aspergillusidone F;
Aspergillusidone C; 2-Chlorounguinol and Aspergillusidone A
Aspergillus unguisCandida albicans[51]
Isoagelasidine B,
Isoagelasine C and
diterpene alkaloids
Sponge Agelas nakamuraiCandida albicans[41]
Ascochlorin/Fimetarin analoguesStilbella fimetariaCandida albicans[52]
Isocoumarin analoguesParaphoma sp. CUGBMF180003Candida albicans[53]
DiketopiperazinesAspergillus versicolor MF180151Candida albicans[54]
Piperazine-trionesDeep-sea-derived Streptomycetes sp. strain SMS636Candida albicans[55]
ChalcomycinsStreptomyces sp. HK-2006-1Candida albicans[56]
Hemimycalins C-ERed Sea Marine Sponge Hemimycale sp.Candida albicans[42]
Thiodiketopiperazine and 3,4-Dihydroisocoumarin DerivativesMarine-Derived Fungus Aspergillus terreusCandida albicans[57]
TurbinmicinSea squirtCandida auris[30]
Alkaloids 6a and 6 bMarine spongeCandida albicans, Candida glabrata, Candida tropicalis, Candida krusei[39]
Table 3. Antifungal activity of marine extracts and sub-products.
Table 3. Antifungal activity of marine extracts and sub-products.
CompoundOriginCandida sp.Reference
Arthrospira platensis extracts by Supercritical carbon dioxide extraction (SFE-CO2)Arthrospira platensisCandida albicans ATCC 10231[60]
Pure fractions from MEF 134Marine endophytic fungi (MEF) 134Candida albicans[61]
Extracts from Corallimorphus cf. pilatus and Stomphia coccineaDeep-Sea Anemones (Corallimorphus cf. pilatus and Stomphia coccinea)Candida albicans[62]
Algae crude extractsMarine macroalgae (Ulva lactuca Linnaeus, Padina gymnospora, Sargassum vulgare, Hypnea musciform, Digenea simplex) Candida albicans, Candida krusei, Candida guilliermondi, Candida parapsilosis[34]
CyanoCoatingCyanobacterium Crocosphaera chwakensis CCY0110Candida albicans[63]
Fish Skin Mucous (FSM)Dasyatis pastinacaCandida albicans ATCC90028, Candida albicans ATCC10231, Candida albicans clinical strain 6, Candida albicans clinical strain 10, Candida glabrata clinical strain 14, Candida tropicalis clinical strain 21[32]
Table 4. Antifungal activity of fatty acids and lipids of marine organisms.
Table 4. Antifungal activity of fatty acids and lipids of marine organisms.
CompoundOriginCandida sp.Reference
Pentadecanoic acidPentadecanalSynthetic originCandida albicans[64]
3-O-β-D-galactopyranosyl-1-O-3,6,9,12,15-octadecapentaenoyl-2-O-tetradecanoylglycerol 1 (MGDG)Karenia mikimotoiCandida albicans[65]
(2S)-3-O-β-D-galactopyranosyl-1-O-3,6,9,12,15-octadecapentaenoylglycerol 2 (MGMG)Karenia mikimotoiCandida albicans[65]
Methyl (3Z,6Z,9Z,12Z,15Z)-octadeca-3,6,9,12,15-pentaenoate 3 (PUFAME)Karenia mikimotoiCandida albicans[65]
Sesquiterpenoids and SteroidsCoral Sinularia brassicaCandida albicans[66]
Oceanalin BSponge Oceanapia sp.Candida glabrata[37]
Marine Polyunsaturated Fatty AcidsSynthetic originCandida albicans and Candida dubliniensis[59]
Oceanapiside (OPS)Marine sponge Oceanapia sp.Candida glabrata[58]
Table 5. Antifungal activity of marine carbohydrates.
Table 5. Antifungal activity of marine carbohydrates.
CompoundOriginCandida sp.Reference
Bengazole AJaspis cf coriaceaCandida albicans[67]
Isocoumarin analoguesParaphoma sp. CUGBMF180003Candida albicans[53]
ExopolysaccharidePorphyridium marinumCandida albicans[68]
Agarose oligosaccharideMarine red algaeCandida albicans[69]
Alginate-chitosan oligosaccharideOcean algaeCandida albicans[70]
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Alves, A.M.C.V.; Cruz-Martins, N.; Rodrigues, C.F. Marine Compounds with Anti-Candida sp. Activity: A Promised “Land” for New Antifungals. J. Fungi 2022, 8, 669.

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Alves AMCV, Cruz-Martins N, Rodrigues CF. Marine Compounds with Anti-Candida sp. Activity: A Promised “Land” for New Antifungals. Journal of Fungi. 2022; 8(7):669.

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Alves, Anelise Maria Costa Vasconcelos, Natália Cruz-Martins, and Célia Fortuna Rodrigues. 2022. "Marine Compounds with Anti-Candida sp. Activity: A Promised “Land” for New Antifungals" Journal of Fungi 8, no. 7: 669.

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