Azoles de antes y ahora: una revisión

Nócua-Báez, Laura Cristina; Uribe-Jerez, Paula; Tarazona-Guaranga, Leonardo; Robles, Ricardo; Cortés, Jorge Alberto

doi:10.4067/s0716-10182020000300219

Cited by 20 publications

(12 citation statements)

References 44 publications

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“…Antifungals used in clinical practice, such as fluconazole and voriconazole, also operate through this same mechanism, inhibiting enzymes vital for fungal growth. This mechanism of action is widely recognized and employed in antifungal therapy [98].…”

Section: Discussionmentioning

confidence: 99%

Streptomyces: a natural source of anti-Candida agents

Martins,

Rodrigues da Silva,

Ratcliffe

et al. 2023

Journal of Medical Microbiology

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Introduction. There is an urgent need to source new compounds that can combat the current threat of serious infection caused by Candida spp. and contend with the problem of antimicrobial resistance. Gap. A synthesis of the evidence available from the current literature is needed to identify promising antifungal chemotherapeutics. Aim. To highlight anti-Candida compounds derived from Streptomyces spp. (a well-known source of antimicrobial compounds) that could translate to potential candidates for future clinical practice. Methodology. A comprehensive review was conducted across three scientific literature databases spanning a 13-year period. Results. We identified 151 compounds with anti-Candida activity. Amongst these, 40 were reported with very strong inhibitory activity, having minimum inhibitory concentrations (MICs) against Candida spp. of <3.5 µg ml−1, 66 compounds were considered strong inhibitors and 45 compounds exhibited moderate inhibitory potential. From an analysis of the MICs, we deduced that the actinomycin-like compounds RSP01 and RSP02 were probably the most promising anti-Candida compounds. Other antifungals of note included filipin-like compounds, which demonstrated superior inhibition to amphotericin B and activity against Candida glabrata and Candida krusei, and bafilomycin derivatives, which had substantial inhibition against Candida parapsilosis. Conclusion. It is essential to recognize the limitations inherent in the quest for new antifungals, which encompass toxicity, in vivo effectiveness and constraints associated with limited data access. However, further investigation through in-depth study and emerging technologies is of paramount importance, given that there are still many more compounds to discover. This review highlights the importance of antifungal compounds derived from Streptomyces , which demonstrate robust inhibition, and, in many cases, low toxicity, making them promising candidates for the development of novel antifungal agents.

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Section: Discussionmentioning

confidence: 99%

Streptomyces: a natural source of anti-Candida agents

Martins,

Rodrigues da Silva,

Ratcliffe

et al. 2023

Journal of Medical Microbiology

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“…Most of the drugs with antifungal activity identified for the first time in this study present fungistatic activity. Azoles, the currently most used antifungal class to treat human fungal infections, acting on ergosterol biosynthesis, 9 are also fungistatic against most pathogenic fungi. 41 The lack of morphological changes caused by hit drugs with off-label antifungal activity in the fungi studied may indicate mechanisms of action not associated with cellular apoptosis, lysis or disruption, which is in accordance with the fungistatic nature of most hit drugs discussed before.…”

Section: Discussionmentioning

confidence: 99%

“… 8 The azoles, which include fluconazole, itraconazole, and posaconazole, inhibit the 14α-sterol-demethylase, altering the functionality of fungal membrane. 9 Flucytosine is an antimetabolite agent that disrupts protein synthesis and must be used in combination with other antifungal drugs, due to the risk of acquired resistance. 10 The echinocandins were the last approved antifungal drug class that acts on the fungal cell-wall, inhibiting the biosynthesis of β-(1,3)-D-glucan.…”

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confidence: 99%

Medicines for Malaria Venture COVID Box: a source for repurposing drugs with antifungal activity against human pathogenic fungi

Almeida‐Paes

Andrade

Ramos

et al. 2021

Mem. Inst. Oswaldo Cruz

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“…albicans is widely used as an important resource for comprehending host-pathogenic interactions, determining therapeutic targets, and acting as a paradigm for the development of novel antifungal agents [31]. Several clinically effective antifungal drugs with different modes of action are available against superficial and systemic infections caused by various species of Candida [32,33]. AmB, a broad-spectrum antifungal drug is becoming more important for fungal infections that are resistant to the first-line azole treatment [34,35].…”

Section: Introductionmentioning

confidence: 99%

Antifungal drug resistance in Candida: a special emphasis on amphotericin B

Ahmady,

Gothwal,

Mukkoli

et al. 2024

APMIS

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Invasive fungal infections in humans caused by several Candida species, increased considerably in immunocompromised or critically ill patients, resulting in substantial morbidity and mortality. Candida albicans is the most prevalent species, although the frequency of these organisms varies greatly according to geographic region. Infections with C. albicans and non‐albicans Candida species have become more common, especially in the past 20 years, as a result of aging, immunosuppressive medication use, endocrine disorders, malnourishment, extended use of medical equipment, and an increase in immunogenic diseases. Despite C. albicans being the species most frequently associated with human infections, C. glabrata, C. parapsilosis, C. tropicalis, and C. krusei also have been identified. Several antifungal drugs with different modes of action are approved for use in clinical settings to treat fungal infections. However, due to the common eukaryotic structure of humans and fungi, only a limited number of antifungal drugs are available for therapeutic use. Furthermore, drug resistance in Candida species has emerged as a result of the growing use of currently available antifungal drugs against fungal infections. Amphotericin B (AmB), a polyene class of antifungal drugs, is mainly used for the treatment of serious systemic fungal infections. AmB interacts with fungal plasma membrane ergosterol, triggering cellular ion leakage via pore formation, or extracting the ergosterol from the plasma membrane inducing cellular death. AmB resistance is primarily caused by changes in the content or structure of ergosterol. This review summarizes the antifungal drug resistance exhibited by Candida species, with a special focus on AmB.

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Azoles de antes y ahora: una revisión

Cited by 20 publications

References 44 publications

Streptomyces: a natural source of anti-Candida agents

Streptomyces: a natural source of anti-Candida agents

Medicines for Malaria Venture COVID Box: a source for repurposing drugs with antifungal activity against human pathogenic fungi

Antifungal drug resistance in Candida: a special emphasis on amphotericin B

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