Insights into Natural Products from Marine-Derived Fungi with Antimycobacterial Properties: Opportunities and Challenges
Tuberculosis (TB) poses a persistent global health threat exacerbated by the emergence of drug-resistant strains; hence, there is a continuous quest for novel antimicrobial agents. Despite efforts to develop effective therapies, existing treatments require a relatively long duration of therapy to er...
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MDPI AG
2025-07-01
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| Series: | Marine Drugs |
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| Online Access: | https://www.mdpi.com/1660-3397/23/7/279 |
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| author | Muhammad Azhari Novi Merliani Marlia Singgih Masayoshi Arai Elin Julianti |
| author_facet | Muhammad Azhari Novi Merliani Marlia Singgih Masayoshi Arai Elin Julianti |
| author_sort | Muhammad Azhari |
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| description | Tuberculosis (TB) poses a persistent global health threat exacerbated by the emergence of drug-resistant strains; hence, there is a continuous quest for novel antimicrobial agents. Despite efforts to develop effective therapies, existing treatments require a relatively long duration of therapy to eradicate the pathogen due to its virulence factors, pathogenesis patterns, and ability to enter dormant states. This can lead to a higher risk of treatment failure due to poor patient adherence to the complex regimen. As a result, considerable research is necessary to identify alternative antituberculosis agents. The marine environment, particularly marine-derived fungi, has recently gained interest due to its potential as an abundant source of bioactive natural products. This review covers 19 genera of marine-derived fungi and 139 metabolites, 131 of which exhibit antimycobacterial activity. The integrated dataset pinpoints the fungal genera and chemical classes that most frequently yield potent antimycobacterial hits while simultaneously exposing critical gaps, such as the minimal evaluation of compounds against dormant bacilli and the presence of underexplored ecological niches and fungal genera. Several compounds exhibit potent activity through uncommon mechanisms, including the inhibition of mycobacterial protein tyrosine phosphatases (MptpB/MptpA), protein kinase PknG, ATP synthase and the disruption of mycobacterial DNA via G-quadruplex stabilization. Structure–activity relationship (SAR) trends are highlighted for the most potent agents, illuminating how specific functional groups underpin target engagement and potency. This review also briefly proposes a dereplication strategy and approaches for toxicity mitigation in the exploration of marine-derived fungi’s natural products. Through this analysis, we offer insights into the potency and challenges of marine-derived fungi’s natural products as hit compounds or scaffolds for further antimycobacterial research. |
| format | Article |
| id | doaj-art-cff2ae6e204c49bfbaa61c52bc5b623f |
| institution | Matheson Library |
| issn | 1660-3397 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | MDPI AG |
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| series | Marine Drugs |
| spelling | doaj-art-cff2ae6e204c49bfbaa61c52bc5b623f2025-07-25T13:28:49ZengMDPI AGMarine Drugs1660-33972025-07-0123727910.3390/md23070279Insights into Natural Products from Marine-Derived Fungi with Antimycobacterial Properties: Opportunities and ChallengesMuhammad Azhari0Novi Merliani1Marlia Singgih2Masayoshi Arai3Elin Julianti4School of Pharmacy, Bandung Institute of Technology, Jl. Ganesha No. 10, Bandung 40132, IndonesiaSchool of Pharmacy, Bandung Institute of Technology, Jl. Ganesha No. 10, Bandung 40132, IndonesiaSchool of Pharmacy, Bandung Institute of Technology, Jl. Ganesha No. 10, Bandung 40132, IndonesiaLaboratory of Natural Products for Drug Discovery, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Osaka 565-0871, JapanSchool of Pharmacy, Bandung Institute of Technology, Jl. Ganesha No. 10, Bandung 40132, IndonesiaTuberculosis (TB) poses a persistent global health threat exacerbated by the emergence of drug-resistant strains; hence, there is a continuous quest for novel antimicrobial agents. Despite efforts to develop effective therapies, existing treatments require a relatively long duration of therapy to eradicate the pathogen due to its virulence factors, pathogenesis patterns, and ability to enter dormant states. This can lead to a higher risk of treatment failure due to poor patient adherence to the complex regimen. As a result, considerable research is necessary to identify alternative antituberculosis agents. The marine environment, particularly marine-derived fungi, has recently gained interest due to its potential as an abundant source of bioactive natural products. This review covers 19 genera of marine-derived fungi and 139 metabolites, 131 of which exhibit antimycobacterial activity. The integrated dataset pinpoints the fungal genera and chemical classes that most frequently yield potent antimycobacterial hits while simultaneously exposing critical gaps, such as the minimal evaluation of compounds against dormant bacilli and the presence of underexplored ecological niches and fungal genera. Several compounds exhibit potent activity through uncommon mechanisms, including the inhibition of mycobacterial protein tyrosine phosphatases (MptpB/MptpA), protein kinase PknG, ATP synthase and the disruption of mycobacterial DNA via G-quadruplex stabilization. Structure–activity relationship (SAR) trends are highlighted for the most potent agents, illuminating how specific functional groups underpin target engagement and potency. This review also briefly proposes a dereplication strategy and approaches for toxicity mitigation in the exploration of marine-derived fungi’s natural products. Through this analysis, we offer insights into the potency and challenges of marine-derived fungi’s natural products as hit compounds or scaffolds for further antimycobacterial research.https://www.mdpi.com/1660-3397/23/7/279tuberculosismarine-derived funginatural productsantimycobacterialdormant |
| spellingShingle | Muhammad Azhari Novi Merliani Marlia Singgih Masayoshi Arai Elin Julianti Insights into Natural Products from Marine-Derived Fungi with Antimycobacterial Properties: Opportunities and Challenges Marine Drugs tuberculosis marine-derived fungi natural products antimycobacterial dormant |
| title | Insights into Natural Products from Marine-Derived Fungi with Antimycobacterial Properties: Opportunities and Challenges |
| title_full | Insights into Natural Products from Marine-Derived Fungi with Antimycobacterial Properties: Opportunities and Challenges |
| title_fullStr | Insights into Natural Products from Marine-Derived Fungi with Antimycobacterial Properties: Opportunities and Challenges |
| title_full_unstemmed | Insights into Natural Products from Marine-Derived Fungi with Antimycobacterial Properties: Opportunities and Challenges |
| title_short | Insights into Natural Products from Marine-Derived Fungi with Antimycobacterial Properties: Opportunities and Challenges |
| title_sort | insights into natural products from marine derived fungi with antimycobacterial properties opportunities and challenges |
| topic | tuberculosis marine-derived fungi natural products antimycobacterial dormant |
| url | https://www.mdpi.com/1660-3397/23/7/279 |
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