β-Carboline Alkaloids From the Deep-Sea Fungus Trichoderma sp. MCCC 3A01244 as a New Type of Anti-pulmonary Fibrosis Agent That Inhibits TGF-β/Smad Signaling Pathway

Hao, Mengjiao; Chen, Pei-Nan; Li, Hou-Jin; Wu, Feng; Zhang, Guangyu; Shao, Zongze; Liu, Xiupian; Ma, Wenzhe; Xu, Jun; Mahmud, Taifo; Lan, Wen‐Jian

doi:10.3389/fmicb.2022.947226

Cited by 16 publications

(16 citation statements)

References 53 publications

(56 reference statements)

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“…; however, β-carboline type of structures was isolated before from a deep-sea fungus, Trichoderma sp. (Hao et al, 2022). Meanwhile, oxindole type of alkaloids was reported in numerous studies from Penicillium sp.…”

Section: Discussionmentioning

confidence: 99%

Antibacterial and cytotoxic secondary metabolites from endophytic fungi associated with Antidesma bunius leaves

Ariantari¹,

Putra²,

Leliqia³

et al. 2023

J Appl Pharm Sci

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Endophytic fungi isolated from Antidesma bunius leaves were investigated in this study. Six fungal endophytes were identified as Penicillium steckii AAB-01, Nemania bipapillata AAB-02, Xylaria feejeensis AAB-03, Hypomontagnella monticulosa AAB-04, Daldinia eschscholtzii AAB-05, and Phyllosticta capitalensis AAB-06. All of the isolated endophytic fungi were subjected to fermentation on rice media, followed by extraction with ethyl acetate. When tested for antibacterial activity, P. steckii AAB-01 extract showed the most potent inhibition against Staphylococcus aureus ATCC 6538 and Staphylococcus epidermidis ATCC 12228. Toxicity screening employing brine shrimp lethality test (BSLT) revealed potential toxicity of P. steckii AAB-01 and X. feejeensis AAB-03 extracts. Further investigation showed P. steckii AAB-01 extract had the highest inhibition toward MCF-7 cells, while D. eschscholtzii AAB-05 extract revealed the strongest cytotoxicity against 4T1 cells. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis tentatively identified five compounds, where indole acetic acid, O-acetylharmol, and oxindole I were suggested as the major metabolites in P. steckii AAB-01 extract, while 6-hydroxymelatonin and 2-methyl-6pentadecylpyridine were suggested as the major metabolites in D. eschscholtzii AAB-05 extract. This is the first report on LC-MS/MS identification of the main metabolites from bioactive extracts of P. steckii AAB-01 and D. eschscholtzii AAB-05 isolated from the leaves of A. bunius, which might contribute to the antibacterial and cytotoxic properties of the extracts. Thus, a detailed investigation of antibacterial and cytotoxic metabolites from these endophytes merits further studies.

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Section: Discussionmentioning

confidence: 99%

Antibacterial and cytotoxic secondary metabolites from endophytic fungi associated with Antidesma bunius leaves

Ariantari¹,

Putra²,

Leliqia³

et al. 2023

J Appl Pharm Sci

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“…Moreover, a newly identified β-carboline alkaloid from the deep-sea fungus Trichoderma sp. MCCC 3A01244 has been shown to decrease pulmonary fibrosis by inhibiting the TGF-β/Smad signaling pathway [ 59 ]. The n-alkylindole was the third indole alkaloid natural product that inhibited the M pro protease activity in our in vitro analysis.…”

Section: Discussionmentioning

confidence: 99%

Virtual and In Vitro Screening of Natural Products Identifies Indole and Benzene Derivatives as Inhibitors of SARS-CoV-2 Main Protease (Mpro)

Ang

Kendall

Atamian

2023

Biology

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The rapid spread of the coronavirus disease 2019 (COVID-19) resulted in serious health, social, and economic consequences. While the development of effective vaccines substantially reduced the severity of symptoms and the associated deaths, we still urgently need effective drugs to further reduce the number of casualties associated with SARS-CoV-2 infections. Machine learning methods both improved and sped up all the different stages of the drug discovery processes by performing complex analyses with enormous datasets. Natural products (NPs) have been used for treating diseases and infections for thousands of years and represent a valuable resource for drug discovery when combined with the current computation advancements. Here, a dataset of 406,747 unique NPs was screened against the SARS-CoV-2 main protease (Mpro) crystal structure (6lu7) using a combination of ligand- and structural-based virtual screening. Based on 1) the predicted binding affinities of the NPs to the Mpro, 2) the types and number of interactions with the Mpro amino acids that are critical for its function, and 3) the desirable pharmacokinetic properties of the NPs, we identified the top 20 candidates that could potentially inhibit the Mpro protease function. A total of 7 of the 20 top candidates were subjected to in vitro protease inhibition assay and 4 of them (4/7; 57%), including two beta carbolines, one N-alkyl indole, and one Benzoic acid ester, had significant inhibitory activity against Mpro protease. These four NPs could be developed further for the treatment of COVID-19 symptoms.

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“…Furthermore, cultivation of a deep-sea fungus, Trichoderma sp. MCCC 3A01244, yielded two β-carboline alkaloids, trichocarbolines A ( 260 ) and C ( 261 ) . Compound 260 displayed efficient antipulmonary fibrosis activity by inhibiting extracellular matrix (ECM) deposition.…”

Section: Secondary Metabolitesmentioning

confidence: 99%

“…MCCC 3A01244, yielded two β-carboline alkaloids, trichocarbolines A (260) and C (261). 107 Compound 260 displayed efficient antipulmonary fibrosis activity by inhibiting extracellular matrix (ECM) deposition. The structures of other alkaloids 251−261 and the representative bioactive compounds are shown in Figure S13 and Figure 5, respectively.…”

Section: Cycloneranementioning

confidence: 99%

Structures and Biological Activities of Secondary Metabolites from the Trichoderma genus (Covering 2018–2022)

Guo,

Shi,

Wang

et al. 2023

J. Agric. Food Chem.

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Trichoderma, a genus with more than 400 species, has a long history of use as an industrial bioreactor, biofertilizer, and biocontrol agent. It is considered a significant source of secondary metabolites (SMs) that possess unique structural features and a wide range of bioactivities. In recent years, numerous secondary metabolites of Trichoderma, including terpenoids, polyketides, peptides, alkaloids, and steroids, have been identified. Most of these SMs displayed antimicrobial, cytotoxic, and antifungal effects. This review focuses on the structural diversity, biological activities, and structure–activity relationships (SARs) of the SMs isolated from Trichoderma covered from 2018 to 2022. This study provides insights into the exploration and utilization of bioactive compounds from Trichoderma species in the agriculture or pharmaceutical industry.

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β-Carboline Alkaloids From the Deep-Sea Fungus Trichoderma sp. MCCC 3A01244 as a New Type of Anti-pulmonary Fibrosis Agent That Inhibits TGF-β/Smad Signaling Pathway

Cited by 16 publications

References 53 publications

Antibacterial and cytotoxic secondary metabolites from endophytic fungi associated with Antidesma bunius leaves

Antibacterial and cytotoxic secondary metabolites from endophytic fungi associated with Antidesma bunius leaves

Virtual and In Vitro Screening of Natural Products Identifies Indole and Benzene Derivatives as Inhibitors of SARS-CoV-2 Main Protease (Mpro)

Structures and Biological Activities of Secondary Metabolites from the Trichoderma genus (Covering 2018–2022)

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