Polyketides produced by the entomopathogenic fungus Metarhizium anisopliae induce Candida albicans growth

Sbaraini, Nicolau; Hu, Jinyu; Roux, Indra; Phan, Chin Soon; Motta, Heryk; Rezaee, Hamideh; Schrank, Augusto; Chooi, Yit‐Heng; Staats, Charley Christian

doi:10.1016/j.fgb.2021.103568

Cited by 12 publications

(11 citation statements)

References 64 publications

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“…The final concentrations of compound 5 in the assay were: 0.568 ng/µL, 1.13 ng/µL, and 2.27 ng/µL; compound 7 final concentrations were: 5.68 ng/µL, 11.3 ng/µL, and 22.7 ng/µL; and compound 9 final concentrations were: 2.84 ng/µL, 5.68 ng/µL, and 11.3 ng/µL. Quantification of the samples was based on the relative fluorescence units (RFU) using the previously established standard curve 12 , 52 .…”

Section: Methodsmentioning

confidence: 99%

Scaffold repositioning of spiro-acridine derivatives as fungi chitinase inhibitor by target fishing and in vitro studies

Viana

Souza

Sbaraini

et al. 2023

Sci Rep

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The concept of “one target, one drug, one disease” is not always true, as compounds with previously described therapeutic applications can be useful to treat other maladies. For example, acridine derivatives have several potential therapeutic applications. In this way, identifying new potential targets for available drugs is crucial for the rational management of diseases. Computational methodologies are interesting tools in this field, as they use rational and direct methods. Thus, this study focused on identifying other rational targets for acridine derivatives by employing inverse virtual screening (IVS). This analysis revealed that chitinase enzymes can be potential targets for these compounds. Subsequently, we coupled molecular docking consensus analysis to screen the best chitinase inhibitor among acridine derivatives. We observed that 3 compounds displayed potential enhanced activity as fungal chitinase inhibitors, showing that compound 5 is the most active molecule, with an IC50 of 0.6 ng/µL. In addition, this compound demonstrated a good interaction with the active site of chitinases from Aspergillus fumigatus and Trichoderma harzianum. Additionally, molecular dynamics and free energy demonstrated complex stability for compound 5. Therefore, this study recommends IVS as a powerful tool for drug development. The potential applications are highlighted as this is the first report of spiro-acridine derivatives acting as chitinase inhibitors that can be potentially used as antifungal and antibacterial candidates.

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Section: Methodsmentioning

confidence: 99%

Scaffold repositioning of spiro-acridine derivatives as fungi chitinase inhibitor by target fishing and in vitro studies

Viana

Souza

Sbaraini

et al. 2023

Sci Rep

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“…Compound 5 was added at the following concentrations: 0.0625, 0.125 and 0.25 µg; compound 7 was added at the following concentrations: 0.625, 1.25 and 2.5 µg; and compound 9 was added at the following concentrations: 0.3125, 0.625 and 1.25 µg. Quanti cation of the samples was based on the relative uorescence units (RFU) using the previously established standard curve [12,57].…”

Section: Chitinolytic Activity Assaysmentioning

confidence: 99%

Identification of spiro-acridine derivatives as fungi chitinase inhibitor by target fishing and in vitro studies

Viana

Souza

Sbaraini

et al. 2022

Preprint

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The concept of “one target, one drug, one disease” is not always true, as compounds with previously described therapeutic applications can be useful to treat other maladies. Acridine derivatives have several potential therapeutic applications. In this way, identifying new potential targets for available drugs is crucial for the rational management of diseases. Computational methodologies are interesting tools in this field, using rational and direct methods. Thus, this study focused on identifying other rational targets for acridine derivatives by employing inverse virtual screening (IVS). This analysis revealed that chitinase enzymes can be potential targets for these compounds. Subsequently, we coupled molecular docking consensus analysis to screen the best chitinase inhibitor among the acridine derivatives. We observed that 3 compounds displayed potential enhanced activity as fungal chitinase inhibitors, showing that compound 5 is the most active molecule, with an IC50 of 0.07 µg. In addition, this compound demonstrated a good interaction with the active site of chitinases from Aspergillus fumigatus and Trichoderma harzianum. Therefore, this study recommends IVS as a powerful tool for drug development. The potential applications are highlighted as this is the first report of spiro-acridine derivatives acting as chitinase inhibitors that can be potentially used as antifungal and antibacterial candidates.

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“…The regulatory function of this type of region is still unclear. 5 Gene designations are based on those from Penicillium aethiopicum [67]. SM = secondary metabolite, PSTF = pathway specific transcription factor, NRPS = nonribosomal peptide synthetase, HR-PKS = highly reducing polyketide synthase, NR-PKS = non-reducing polyketide synthase, PR-PKS = partially reducing polyketide synthase, DMATS = dimethylallyltryptophan synthase, TC = terpene cyclase, ICS = isocyanide synthase.…”

Section: Aspergillus Fumigatusmentioning

confidence: 99%

“…3 No conserved domain means PSTF without conserved domain. 4 TAFC = triacetylfusarinine C. 5 Two PSTFs are not located in a single cluster. 6 Key enzyme gene involved in the L-tyrosine degradation pathway encoding 4-hydroxyphenylpyruvate dioxygenase.…”

Section: Aspergillus Fumigatusmentioning

confidence: 99%

“…Secondary metabolites (SMs) in fungi, also known as natural products, are present and synthesized in ecologically diverse species [1]. In fungi, SMs can provide self-protection and act as mediators for communication with other organisms or as virulence factors during pathogenic interactions with plants and animals [2][3][4][5][6]. Many SMs were proven to be associated with potentially useful biologic activities [7,8].…”

Section: Introductionmentioning

confidence: 99%

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Presence, Mode of Action, and Application of Pathway Specific Transcription Factors in Aspergillus Biosynthetic Gene Clusters

Wang

Keller

et al. 2021

IJMS

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Fungal secondary metabolites are renowned toxins as well as valuable sources of antibiotics, cholesterol-lowering drugs, and immunosuppressants; hence, great efforts were levied to understand how these compounds are genetically regulated. The genes encoding for the enzymes required for synthesizing secondary metabolites are arranged in biosynthetic gene clusters (BGCs). Often, BGCs contain a pathway specific transcription factor (PSTF), a valuable tool in shutting down or turning up production of the BGC product. In this review, we present an in-depth view of PSTFs by examining over 40 characterized BGCs in the well-studied fungal species Aspergillus nidulans and Aspergillus fumigatus. Herein, we find BGC size is a predictor for presence of PSTFs, consider the number and the relative location of PSTF in regard to the cluster(s) regulated, discuss the function and the evolution of PSTFs, and present application strategies for pathway specific activation of cryptic BGCs.

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Polyketides produced by the entomopathogenic fungus Metarhizium anisopliae induce Candida albicans growth

Cited by 12 publications

References 64 publications

Scaffold repositioning of spiro-acridine derivatives as fungi chitinase inhibitor by target fishing and in vitro studies

Scaffold repositioning of spiro-acridine derivatives as fungi chitinase inhibitor by target fishing and in vitro studies

Identification of spiro-acridine derivatives as fungi chitinase inhibitor by target fishing and in vitro studies

Presence, Mode of Action, and Application of Pathway Specific Transcription Factors in Aspergillus Biosynthetic Gene Clusters

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