Screening of potential filamentous fungi Aspergillus sp for biotransformation of quercetin

Dewi, Rizna Triana; Fitria, Irni; Minarti, Minarti; Sundowo, Andini; Nuriyah, Lailiyatin; Fajriah, Sofa; Lotulung, Puspa Dewi; Darmawan, Akhmad

doi:10.1063/1.5064303

Cited by 3 publications

(1 citation statement)

References 9 publications

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“…Reported α-glucosidase activities regarding several A. terrus-isolated metabolites within our literature review [52][53][54][55][56][57][58][59] have prompted us to further investigate the potentiality of identifying novel uncited hits with potential biological activity. Additionally, exploring the molecular aspects of the compound's affinity/binding with human α-glucosidase biological targets through a sophisticated in silico study was rationalized in order to guide future lead optimization and development.…”

Section: Molecular Docking Analysismentioning

confidence: 99%

Deciphering Molecular Aspects of Potential α-Glucosidase Inhibitors within Aspergillus terreus: A Computational Odyssey of Molecular Docking-Coupled Dynamics Simulations and Pharmacokinetic Profiling

Elhady,

Alshobaki,

Elfaky

et al. 2023

Metabolites

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Hyperglycemia, as a hallmark of the metabolic malady diabetes mellitus, has been an overwhelming healthcare burden owing to its high rates of comorbidity and mortality, as well as prospective complications affecting different body organs. Available therapeutic agents, with α-glucosidase inhibitors as one of their cornerstone arsenal, control stages of broad glycemia while showing definitive characteristics related to their low clinical efficiency and off-target complications. This has propelled the academia and industrial section into discovering novel and safer candidates. Herein, we provided a thorough computational exploration of identifying candidates from the marine-derived Aspergillus terreus isolates. Combined structural- and ligand-based approaches using a chemical library of 275 metabolites were adopted for pinpointing promising α-glucosidase inhibitors, as well as providing guiding insights for further lead optimization and development. Structure-based virtual screening through escalating precision molecular docking protocol at the α-glucosidase canonical pocket identified 11 promising top-docked hits, with several being superior to the market drug reference, acarbose. Comprehensive ligand-based investigations of these hits’ pharmacokinetics ADME profiles, physiochemical characterizations, and obedience to the gold standard Lipinski’s rule of five, as well as toxicity and mutagenicity profiling, proceeded. Under explicit conditions, a molecular dynamics simulation identified the top-stable metabolites: butyrolactone VI (SK-44), aspulvinone E (SK-55), butyrolactone I 4′’’’-sulfate (SK-72), and terrelumamide B (SK-173). They depicted the highest free binding energies and steadiest thermodynamic behavior. Moreover, great structural insights have been revealed, including the advent of an aromatic scaffold-based interaction for ligand–target complex stability. The significance of introducing balanced hydrophobic/polar moieties, like triazole and other bioisosteres of carboxylic acid, has been highlighted across docking, ADME/Tox profiling, and molecular dynamics studies for maximizing binding interactions while assuring safety and optimal pharmacokinetics for targeting the intestinal-localized α-glucosidase enzyme. Overall, this study provided valuable starting points for developing new α-glucosidase inhibitors based on nature-derived unique scaffolds, as well as guidance for prospective lead optimization and development within future pre-clinical and clinical investigations.

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Section: Molecular Docking Analysismentioning

confidence: 99%

Deciphering Molecular Aspects of Potential α-Glucosidase Inhibitors within Aspergillus terreus: A Computational Odyssey of Molecular Docking-Coupled Dynamics Simulations and Pharmacokinetic Profiling

Elhady,

Alshobaki,

Elfaky

et al. 2023

Metabolites

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Bioconversion of quercetin glucosides from Dendrophthoe pentandra leaf using Aspergillus acueletus LS04-3

Dewi¹,

Ekapratiwi²,

Sundowo³

et al. 2019

Proceedings of the 5th International Symposium on Applied Chemistry 2019

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Phytochemical Constituent’s Comparison Using Various Drying Effects on Rubus Fraxinifolius Pour Leaves

et al. 2019

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Rubus fraxinifolius is a genus that belongs to the Rosaceae family, which grows in the mountainous forests in Indonesia. The study aimed to determine the effects of air-drying (AD) and oven drying (OD) of the young R. fraxinifolius leaves and compare them to the fresh leaves (FL) to observe the phytochemical content and bioactivities. Phytochemical contents of the samples were determined based on qualitative assay, total phenolics, and total flavonoid, whereas bioactivities were evaluated on antioxidant DPPH free radical scavenging effect, α-glucosidase inhibitory activity, and antibacterial assays. LCMS-MS was used for the quantitative investigation of naturally occurring phytochemicals. The methanol exttract of FL had the highest free radical scavenging activity against DPPH with IC50of 45.51± 5.03µg/mL, total phenolic content (25.35 ± 1.06 mg GAE/100 mg extract), and total flavonoid content (28.71 ± 2.07 equivalent quercetin mg/ 100 mg extract) compared to those of AD and OD. However, AD had the highest α-glucosidase inhibitory activity (IC50= 8.86 ± 1.41µg/mL) among others. The antibacterial activity of the young leaves showed that there was no activity difference in both fresh and dried conditions. Based on LCMS-MS analysis, it was revealed that Luteolin-7-O-glucoronide, an active antioxidant flavonoid glycoside, had been detected in FL and AD leaf extracts, but it was not found in OD leaf extract. Our ﬁndings showed that drying could influence the phytochemical contents, which significantly affect the production of characteristic active compounds in R. fraxinifolius leaves.

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Screening of potential filamentous fungi Aspergillus sp for biotransformation of quercetin

Cited by 3 publications

References 9 publications

Deciphering Molecular Aspects of Potential α-Glucosidase Inhibitors within Aspergillus terreus: A Computational Odyssey of Molecular Docking-Coupled Dynamics Simulations and Pharmacokinetic Profiling

Deciphering Molecular Aspects of Potential α-Glucosidase Inhibitors within Aspergillus terreus: A Computational Odyssey of Molecular Docking-Coupled Dynamics Simulations and Pharmacokinetic Profiling

Bioconversion of quercetin glucosides from Dendrophthoe pentandra leaf using Aspergillus acueletus LS04-3

Phytochemical Constituent’s Comparison Using Various Drying Effects on Rubus Fraxinifolius Pour Leaves

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