Newly synthesised oxime and lactone derivatives from <i>Dipterocarpus alatus</i> dipterocarpol as anti-diabetic inhibitors: experimental bioassay-based evidence and theoretical computation-based prediction

Thảo, Trần Thị Phương; Bui, Thanh Q.; Hai, Nguyen Thi Thanh; Huynh, Lam K.; Quy, Phan Tu; Bảo, Nguyễn Chí; Dung, Nguyễn Thị; Linh, Nguyen Thi Thuy; Loc, Tran Van; Смирнова, И. Е.; Petrova, А. V.; Ninh, Phạm Thị; Sung, Trần Văn; Nhung, Nguyen Thi Ai

doi:10.1039/d1ra04461c

Cited by 14 publications

(7 citation statements)

References 45 publications

(58 reference statements)

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“…According to the theoretical interpretation as given, the most effective ligand-3W37 inhibitory structures are 8-3W37 (DS −12.9 kcal·mol −1 ; RMSD 1.29 Å) > 4-3W37 (DS −12.3 kcal·mol −1 ; RMSD 1.37 Å); the significance is defined as DS < −12 kcal·mol −1 , which is thought to correspond with the ability to induce effective inhibitory effects. In fact, our preceding works correlated this range with assay-based IC 50 values < 50 μM (control drug IC 50 ca 300 μM), 35,36 which were considered effective inhibition against the enzymatic activity of α-glucosidase. In terms of ligand-PTP1B inhibitory structures, the corresponding order is 8-PTP1B (DS −13.4 kcal·mol −1 ; RMSD 1.75 Å) > 4-PTP1B (DS −13.1 kcal·mol −1 ; RMSD 1.49 Å) > 2-PTP1B (DS −12.9 kcal·mol −1 ; RMSD 1.17 Å); the significance is defined by comparison to the D-PTP1B complex (ie DS −12.8 kcal·mol −1 ; RMSD 1.50 Å).…”

Section: Resultsmentioning

confidence: 94%

In Silico Investigation of Aporphine Alkaloids Isolated From Magnolia coriacea Against α-Glucosidase and Tyrosine Phosphatase 1B

Ninh

Bui

Dung

et al. 2023

Natural Product Communications

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Objective Magnolia coriacea is a rare species of Magnoliaceae and categorized as critically endangered, yet known for its valuable pharmaceutical properties. Phytochemical study of the plant was carried out, and the isolated compounds were subjected to different computational platforms to predict their chemical, inhibitory, physicochemical, and pharmacological properties. Methods M coriacea dried twig or leaf powder was partially extracted with n-hexane, ethyl acetate, and 90% methanol to produce the corresponding extracts, which were subjected to column chromatography. The isolated compounds were identified by nuclear magnetic resonance (NMR) spectroscopic and electrospray ionization mass spectrometry (ESI-MS) methods. Results Eight known aporphine alkaloids were isolated, (+)-glaucine N-oxide (1), N-methyl glaucine acetate (2), (+)-( S)-glaucine (3), magnoflorine (4), pontevedrine (5), O-methylatheroline (6), 7-hydroxydehydroglaucine (7), and mangochinine acetate (8). Quantum-based calculations found no abnormal structural constraints and suggested 2, 4, and 8 as the most promising inhibitors of protein structures in general with intensive nucleophilic reactive sites at their nitrogen atoms. Classical-based docking simulation agrees with this with respect to 3W37 (docking score [DS] < −12 kcal·mol−1) and PTP1B (DS ca −13 kcal·mol−1) structures. The biocompatibility and pharmacokinetics of the three candidates given by quantitative structure–activity relationship (QSAR) and absorption, distribution, metabolism, excretion, and toxicity (ADMET) regressions justify their potential for medicinal development. The results encourage further experimental studies of the promising M coriacea-extracted aporphine alkaloids for drug-developing purposes, especially mangochinine acetate (8). Conclusions Isolation and molecular docking simulation of 8 aporphine alkaloids were accomplished. QSAR and ADMET regressions suggested that three compounds (2, 4, and 8) were the most suitable for medicinal applications given both biocompatibility and pharmacokinetics based on specific prediction toward 3W37 (α-glucosidase) and PTP1B (tyrosine phosphatase 1B) structures.

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Section: Resultsmentioning

confidence: 94%

In Silico Investigation of Aporphine Alkaloids Isolated From Magnolia coriacea Against α-Glucosidase and Tyrosine Phosphatase 1B

Ninh

Bui

Dung

et al. 2023

Natural Product Communications

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“…In the previous investigation [ 53 ], theoretical complexes of the tetrylone family with E HOMO values of − 3 to − 7 eV were also found as highly stable. It has been evidenced that all structures possess an insulation-to-semiconduction energy gap (3.2 eV < EG < 9 eV), showing good intermolecular binding capability toward protein structures [ 54 ], and this was further explained based on the super-exchange theory [ 55 , 56 ] and the electron hopping model [ 57 ]. In this study, the energy gap values of the inhibitors were found in the range of 3.77 to 5.61 eV; as such, they have potential intermolecular binding capability toward the targeting enzyme.…”

Section: Resultsmentioning

confidence: 99%

Novel Anti-Acetylcholinesterase Effect of Euonymus laxiflorus Champ. Extracts via Experimental and In Silico Studies

Nguyen

Wang

Phan

et al. 2023

Life

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Alzheimer’s disease (AD) is the most common form of dementia, which is recorded as a global health issue. Natural acetylcholinesterase inhibitors (AChEIs) are considered a helpful therapy for the management of symptoms of patients with mild-to-moderate AD. This work aimed to investigate and characterize Euonymus laxiflorus Champ. (ELC) as a natural source of AChEIs compounds via in vitro and virtual studies. The screening parts used, including the leaves, heartwood, and trunk bark of ELC, revealed that the trunk bark extract possessed the highest activity, phenolics and flavonoid content. The in vitro anti-Alzheimer activity of ELC trunk bark was notably reclaimed for the first time with comparable effect (IC50 = 0.332 mg/mL) as that of a commercial AChEI, berberine chloride (IC50 = 0.314 mg/mL). Among various solvents, methanol was the most suitable to extract ELC trunk bark with the highest activity. Twenty-one secondary metabolites (1–21) were identified from ELC trunk bark extract, based on GCMS and UHPLC analyses. Of these, 10 volatile compounds were identified from this herbal extract for the first time. One phenolic (11) and seven flavonoid compounds (15–21) were also newly found in this herbal extract. Of the identified compounds, chlorogenic acid (11), epigallocatechin gallate (12), epicatechin (13), apigetrin (18), and quercetin (20) were major compounds with a significant content of 395.8–2481.5 μg/g of dried extract. According to docking-based simulation, compounds (11–19, and 21) demonstrated more effective inhibitory activity than berberine chloride, with good binding energy (DS values: −12.3 to −14.4 kcal/mol) and acceptable RMSD values (0.77–1.75 Å). In general, these identified compounds processed drug properties and were non-toxic for human use, based on Lipinski’s rule of five and ADMET analyses.

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“…If subjected to a nonequivalent reference to our experiment-correlated works on single-enzymatic inhibition, these values might be referred to as effective inhibitors against α-glucosidase (assaying-based IC50 values < 100 μM). 37,38 Therefore, the G. lucidum extracts, in general, and 1 (Butyl lucidenate P), 2 (Butyl lucidenate E2), 11 (Methyl ganoderate H), 13 (Methyl lucidenate N), in particular, are highly recommended for further experimental validation from enzymatic bioassays.…”

Section: Resultsmentioning

confidence: 99%

Combinatory in silico Study on Anti-Diabetic Potential of Ganoderma lucidum Compounds Against α-Glucosidase

2023

TJNPR

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Ganoderma species is excessively well-known for a variety of medicinal effects and health benefits by folk experiences, thus often underestimated for componential specification. Ganoderma lucidum methanol-extracted components (1-15) were selected from the literature and subjected for computational evaluations on the anti-diabetic potentiality. As the results, molecular docking simulation suggests the most promising PDB-3W37 (α-glucosidase) inhibitors from the standpoint of static intermolecular interaction, i.e. 1 (DS -12.8 kcal.mol -1 ; RMSD 1.23 Å) > 2 (DS -12.3 kcal.mol -1 ; RMSD 1.76 Å) > 11 (DS -12.0 kcal.mol -1 ; RMSD 1.20 Å) ≈ 13 (DS -12.1 kcal.mol -1 ; RMSD 1.58 Å); QSARIS confirm their biocompatibility given the physicochemical properties in reference to Lipinski's rule of five; ADMET pharmacokinetics and pharmacology justify their pharmaceutical applicability. Quantum-based retrievals justify their suitability from the view of intrinsic chemical properties, i.e: ground-state energy, dipole moment, and band gap:

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Newly synthesised oxime and lactone derivatives from Dipterocarpus alatus dipterocarpol as anti-diabetic inhibitors: experimental bioassay-based evidence and theoretical computation-based prediction

Abstract: Dipterocarpus alatus-derived products are expected to exhibit anti-diabetes properties.

Cited by 14 publications

References 45 publications

In Silico Investigation of Aporphine Alkaloids Isolated From Magnolia coriacea Against α-Glucosidase and Tyrosine Phosphatase 1B

In Silico Investigation of Aporphine Alkaloids Isolated From Magnolia coriacea Against α-Glucosidase and Tyrosine Phosphatase 1B

Novel Anti-Acetylcholinesterase Effect of Euonymus laxiflorus Champ. Extracts via Experimental and In Silico Studies

Combinatory in silico Study on Anti-Diabetic Potential of Ganoderma lucidum Compounds Against α-Glucosidase

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