Natural Polyketides Act as Promising Antifungal Agents

Wang, Li; Lu, Hui; Jiang, Yuanying

doi:10.3390/biom13111572

Cited by 7 publications

(3 citation statements)

References 102 publications

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“…Azoles have been widely employed as a therapeutic intervention for the treatment of IFDs [5][6][7]. Furthermore, alternative categories of antifungal agents, including polyenes (such as nystatin (1) and amphotericin B (2)), flucytosine (3), and echinocandins (such as anidulafungin (4) and caspofungin (5)), have been utilized for the management of IFDs [8,9]. However, drug-resistant fungal pathogens have emerged as a consequence of antifungal treatment.…”

Section: Introductionmentioning

confidence: 99%

Marine-Derived Metabolites Act as Promising Antifungal Agents

Hang,

Lu,

Jiang

2024

Marine Drugs

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The incidence of invasive fungal diseases (IFDs) is on the rise globally, particularly among immunocompromised patients, leading to significant morbidity and mortality. Current clinical antifungal agents, such as polyenes, azoles, and echinocandins, face increasing resistance from pathogenic fungi. Therefore, there is a pressing need for the development of novel antifungal drugs. Marine-derived secondary metabolites represent valuable resources that are characterized by varied chemical structures and pharmacological activities. While numerous compounds exhibiting promising antifungal activity have been identified, a comprehensive review elucidating their specific underlying mechanisms remains lacking. In this review, we have compiled a summary of antifungal compounds derived from marine organisms, highlighting their diverse mechanisms of action targeting various fungal cellular components, including the cell wall, cell membrane, mitochondria, chromosomes, drug efflux pumps, and several biological processes, including vesicular trafficking and the growth of hyphae and biofilms. This review is helpful for the subsequent development of antifungal drugs due to its summary of the antifungal mechanisms of secondary metabolites from marine organisms.

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Section: Introductionmentioning

confidence: 99%

Marine-Derived Metabolites Act as Promising Antifungal Agents

Hang,

Lu,

Jiang

2024

Marine Drugs

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“…This issue is further compounded by increased drug-resistant fungal infections [ 2 , 3 , 4 ]. While novel approaches may offer potential solutions for treating IFIs [ 5 , 6 ], azoles, functioning as inhibitors of lanosterol 14-α demethylase, continue to hold paramount importance as clinically approved antifungal medications for managing these infections [ 7 ]. Fluconazole (FLC) is a prominent antifungal azole that is extensively utilized in clinical practice owing to its wide-ranging antifungal activity, remarkable safety record, and diverse modes of administration [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Pitavastatin Calcium Confers Fungicidal Properties to Fluconazole by Inhibiting Ubiquinone Biosynthesis and Generating Reactive Oxygen Species

Li,

Feng,

Feng

et al. 2024

Antioxidants

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Fluconazole (FLC) is extensively employed for the prophylaxis and treatment of invasive fungal infections (IFIs). However, the fungistatic nature of FLC renders pathogenic fungi capable of developing tolerance towards it. Consequently, converting FLC into a fungicidal agent using adjuvants assumes significance to circumvent FLC resistance and the perpetuation of fungal infections. This drug repurposing study has successfully identified pitavastatin calcium (PIT) as a promising adjuvant for enhancing the fungicidal activity of FLC from a comprehensive library of 2372 FDA-approved drugs. PIT could render FLC fungicidal even at concentrations as low as 1 μM. The median lethal dose (LD50) of PIT was determined to be 103.6 mg/kg. We have discovered that PIT achieves its synergistic effect by inhibiting the activity of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, thereby impeding ubiquinone biosynthesis, inducing reactive oxygen species (ROS) generation, triggering apoptosis, and disrupting Golgi function. We employed a Candida albicans strain that demonstrated a notable tolerance to FLC to infect mice and found that PIT effectively augmented the antifungal efficacy of FLC against IFIs. This study is an illustrative example of how FDA-approved drugs can effectively eliminate fungal tolerance to FLC.

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“…Invasive fungal diseases (IFDs) are increasingly recognized as a growing concern associated with elevated morbidity and mortality rates, particularly among immunocompromised individuals. , Recent epidemiological data suggests that IFDs are responsible for more than 65 million severe cases and 25 million deaths annually . Nevertheless, the existing antifungal options are constrained and inadequate in effective addressing. , These include polyenes, which directly interact with the fungal membrane ergosterol, echinocandins that inhibit β-1,3-glucan synthase, and azoles that target lanosterol 14-α-demethylase . Furthermore, the escalating resistance of fungi to current drugs, particularly azoles, and the emergence of the highly resistant Candida aruis underscore the critical necessity for the exploration of novel antifungal compounds and the identification of new therapeutic targets.…”

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confidence: 99%

Isobavachalcone Exhibits Potent Antifungal Efficacy by Inhibiting Enolase Activity and Glycolysis in Candida albicans

Wu,

Ji,

Huang

et al. 2024

ACS Infect. Dis.

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Invasive fungal diseases (IFDs) are becoming increasingly acknowledged as a significant concern linked to heightened rates of morbidity and mortality. Regrettably, the available antifungal therapies for managing IFDs are constrained. Emerging evidence indicates that enolase holds promise as a potential target protein for combating IFDs; however, there is currently a deficiency in antifungal medications specifically targeting enolase. This study establishes that isobavachalcone (IBC) exhibits noteworthy antifungal efficacy both in vitro and in vivo. Moreover, our study has demonstrated that IBC effectively targets Eno1 in Candida albicans (CaEno1), resulting in the suppression of the glycolytic pathway. Additionally, our research has indicated that IBC exhibits a higher affinity for CaEno1 compared to human Eno1 (hEno1), with the presence of isoprenoid in the side chain of IBC playing a crucial role in its ability to inhibit enolase activity. These findings contribute to the comprehension of antifungal approaches that target Eno1, identifying IBC as a potential inhibitor of Eno1 in human pathogenic fungi.

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Natural Polyketides Act as Promising Antifungal Agents

Cited by 7 publications

References 102 publications

Marine-Derived Metabolites Act as Promising Antifungal Agents

Marine-Derived Metabolites Act as Promising Antifungal Agents

Pitavastatin Calcium Confers Fungicidal Properties to Fluconazole by Inhibiting Ubiquinone Biosynthesis and Generating Reactive Oxygen Species

Isobavachalcone Exhibits Potent Antifungal Efficacy by Inhibiting Enolase Activity and Glycolysis in Candida albicans

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