Synthesis and Inhibitory Activity of Curculigoside A Derivatives as Potential Anti-Diabetic Agents with β-Cell Apoptosis

Nursamsiar,; Nur, Syamsu; Febrina, Ellin; Asnawi, Aiyi; Syafiie, S.

doi:10.1016/j.molstruc.2022.133292

Cited by 8 publications

(9 citation statements)

References 28 publications

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“…Certain residues, including Asp203, Asp542, Asp327, His600, and Arg526, have been discovered through the studies as being implicated in the inhibitory potential and binding interactions of the curculigoside A derivatives. Furthermore, in vitro investigations into the inhibition of alpha-glucosidase have been undertaken to authenticate the findings obtained in silico (9). The study has provided evidence that these derivatives possess the capacity to function as inhibitors of alpha-glucosidase, a target therapeutic agent in the treatment of type 2 diabetes.…”

Section: Discussionmentioning

confidence: 98%

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Integrative computational approaches for designing novel alpha-glucosidase inhibitors based on curculigoside A derivatives: Virtual screening, molecular docking, and molecular dynamics

Asnawi,

Mieldianisa,

Aligita

et al. 2024

J Herbmed Pharmacol

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Introduction: Over 422 million people worldwide suffer from diabetes, causing 1.5 million fatalities annually. The existing medications have shortcomings, including poor glucose control and adverse effects. The present study aimed to create possible alpha-glucosidase inhibitors utilizing a curculigoside A derivative ligand-based model. Methods: A pharmacophore model was constructed utilizing the structure information of curculigoside A derivatives and PharmaGist. Subsequently, virtual screening, molecular docking, and molecular dynamics were employed to simulate the hits. Results: From six training sets, eleven pharmacophore models were developed; the model with the highest score (18.0435) was chosen for further analysis. Using the verified pharmacophore model, 270 547 chemicals from the ZINC natural product database were subjected to virtual screening. Subsequently, molecular docking was performed on the top 1000 hits with AutoDock Wizard from PyRx. This analysis unveiled 434 hits with better binding energies than acarbose, the native ligand. Subsequently, second optimal docking configurations were evaluated with AutoDock 2.4; this process yielded the discovery of three prospective inhibitors (ZINC000150350051, ZINC000008382292, and ZINC000085595291) characterized by the most advantageous binding energies. To evaluate the stability and dynamics of these ligand-receptor complexes, Gromacs 2022 molecular dynamics simulations were executed for one hundred nanoseconds. Out of the three hits, ZINC000085595291 (Hit03) exhibited good energy components and interaction stability constantly during the simulation. Conclusion: The integrated computational strategy identified promising alpha-glucosidase inhibitors in curculigoside A compounds, highlighting the potential of ZINC000085595291 (Hit03) as a potential diabetes therapeutic agent.

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Section: Discussionmentioning

confidence: 98%

“…The synthesis and inhibitory activity of curculigoside A derivatives have been studied for their potential antidiabetic effects and β-cell apoptosis (9). The synthesis process involves using imidazole as a catalyst and esterification with halogenated carboxylic acids, producing good yields.…”

Section: Introductionmentioning

confidence: 99%

Integrative computational approaches for designing novel alpha-glucosidase inhibitors based on curculigoside A derivatives: Virtual screening, molecular docking, and molecular dynamics

Asnawi,

Mieldianisa,

Aligita

et al. 2024

J Herbmed Pharmacol

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“…The study utilized molecular docking simulations to evaluate the interaction between curculigoside A and its derivatives with α-glucosidase identified the stability of the binding interaction and the role of Asp542 residue in the stability of the binding interaction. 32 Virtual screening simulation using AutoDock A total of 460 VINA hits were further screened using AutoDock 4.2 and used the free energy bonding (∆G) to filter the hits. The ∆G value of the 30 hits was sorted (Table 2) with the smallest value compared to the native ligand to proceed to the interaction visualization.…”

Section: Virtual Screening Using Autodock Binding Site Locationsmentioning

confidence: 99%

Virtual Screening Using a Ligand-based Pharmacophore Model from Ashitaba (Angelica keiskei K.) Isolates and Molecular Docking to Obtained New Candidates as -Glucosidase Inhibitors

2024

TJNPR

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Globally, about 422 million people have diabetes, with the majority living in low-and middle-income countries. Diabetes caused 1.5 million deaths in 2019. 3 Diabetes was the direct cause of 1.5 million deaths in 2019, and 48 % of all deaths due to diabetes occurred before the age of 70 years. Another 460,000 kidney disease deaths were caused by diabetes, and raised blood glucose causes around 20 % of cardiovascular deaths. 4 These statistics highlight the significant impact of DM on individuals and society. The high prevalence of diabetes and prediabetes underscores the need for effective prevention and management strategies. The total number of people living with diabetes is projected to rise to 643 million by 2030 and 783 million by 2045. 5 Over 90 % of people with diabetes have Type 2 Diabetes Mellitus (T2DM), which is driven by socioeconomic, demographic, environmental, and genetic factors. These statistics highlight the significant impact of T2DM on individuals and society. The high prevalence of T2DM underscores the need for effective prevention and management strategies. Acarbose is a pharmacological therapy for T2DM that works by inhibiting the α-glucosidase enzyme. Acarbose is approved for treating adults with T2DM as an adjunct to diet only or diet and exercise, depending on the patient's health status. 6 Acarbose is not a highly effective agent when used as monotherapy, but it is commonly used in

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“…Moreover, computational approaches such as molecular docking simulation and molecular dynamics are adopted mainly to screen potential drugs and molecules from various databases and libraries, saving experimentation costs and time in drug discovery. [9][10][11][12] This research aims to study the affinity, interaction pattern, and stability complex of chemical compounds in celery leaves (Apium graveolens L.) on the structure of the VKORC1 enzyme as a candidate lead compound anticoagulant. We began by searching the literature for plant isolates before moving on to molecular docking and molecular dynamics.…”

Section: Introductionmentioning

confidence: 99%

Prediction of a Stable Complex of Compounds in the Ethanol Extract of Celery Leaves (Apium graveolens L.) Function as a VKORC1 Antagonist

2023

TJNPR

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The vitamin K cycle, specifically the protein VKORC1 (Vitamin K epoxide reductase complex subunit 1), is closely linked to coagulation mechanisms in the body. Disruptions in this cycle will be associated with vascular diseases such as myocardial infarction and stroke. Warfarin is commonly used as an anticoagulant, but it still has side effects in interactions with numerous drug compounds; thus, it is necessary to search for safer candidate compounds. The ethanol extract of celery leaves (Apium graveolens L.) has potential anticoagulant activity, but the compound responsible for this activity has not been identified yet. The CADD method has been developed to predict in silico a compound's potential to interact with binding sites. This study aimed to predict interactions and obtain a stable complex of the compounds in the ethanol extract of celery leaves, which function as a VKORC1 antagonist. A total of 23 compounds were simulated using Autodock 4.2, and AMBER 18 was then used to simulate the stability of the five compounds with the best interactions. The docking simulation results of 17 test compounds (ligands) yielded five selected compounds, namely 6-isopentenyloxy-isobergapten (S1), Heratomin (S2), Apigenin (S3), Lanatin (S4), and Isoimperatorin (S5), with G values of −9.27, −9.26, −9.22, −9.13, and −8.94 kcal/mol, respectively. The MD simulation continued to produce 6-isopentenyloxy-isobergapten as the most effective ligand for stabilizing the complex for 100 ns from these five ligands. In conclusion, the 6-isopentenyloxy-isobergapten from celery leaf has the potential as a candidate anticoagulant, VKORC1.

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Synthesis and Inhibitory Activity of Curculigoside A Derivatives as Potential Anti-Diabetic Agents with β-Cell Apoptosis

Cited by 8 publications

References 28 publications

Integrative computational approaches for designing novel alpha-glucosidase inhibitors based on curculigoside A derivatives: Virtual screening, molecular docking, and molecular dynamics

Integrative computational approaches for designing novel alpha-glucosidase inhibitors based on curculigoside A derivatives: Virtual screening, molecular docking, and molecular dynamics

Virtual Screening Using a Ligand-based Pharmacophore Model from Ashitaba (Angelica keiskei K.) Isolates and Molecular Docking to Obtained New Candidates as -Glucosidase Inhibitors

Prediction of a Stable Complex of Compounds in the Ethanol Extract of Celery Leaves (Apium graveolens L.) Function as a VKORC1 Antagonist

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