Molecular Docking of Xanthone Derivatives as Therapeutic Agent for Covid-19

Yuanita, Emmy; Sudirman, Sudirman; Dharmayani, Ni Komang Tri; Ulfa, Maria; Hadisaputra, Saprizal; Syahri, Jufrizal

doi:10.20884/1.jm.2022.17.1.5600

Cited by 5 publications

(4 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Numerous natural compounds inhibit the SARS-CoV-2 main protease (M pro ) 4 , including flavonoids 5 , 6 , phenolics 7 , 8 , and xanthones 9 . Xanthones such as mangostins and their derivatives are major compounds isolated from mangosteen, which is a fruit widely used in folk medicine in tropical countries.…”

Section: Introductionmentioning

confidence: 99%

Promising SARS-CoV-2 main protease inhibitor ligand-binding modes evaluated using LB-PaCS-MD/FMO

Hengphasatporn

Harada

Wilasluck

et al. 2022

Sci Rep

View full text Add to dashboard Cite

Parallel cascade selection molecular dynamics-based ligand binding-path sampling (LB-PaCS-MD) was combined with fragment molecular orbital (FMO) calculations to reveal the ligand path from an aqueous solution to the SARS-CoV-2 main protease (Mpro) active site and to customise a ligand-binding pocket suitable for delivering a potent inhibitor. Rubraxanthone exhibited mixed-inhibition antiviral activity against SARS-CoV-2 Mpro, relatively low cytotoxicity, and high cellular inhibition. However, the atomic inhibition mechanism remains ambiguous. LB-PaCS-MD/FMO is a hybrid ligand-binding evaluation method elucidating how rubraxanthone interacts with SARS-CoV-2 Mpro. In the first step, LB-PaCS-MD, which is regarded as a flexible docking, efficiently samples a set of ligand-binding pathways. After that, a reasonable docking pose of LB-PaCS-MD is evaluated by the FMO calculation to elucidate a set of protein–ligand interactions, enabling one to know the binding affinity of a specified ligand with respect to a target protein. A possible conformation was proposed for rubraxanthone binding to the SARS-CoV-2 Mpro active site, and allosteric inhibition was elucidated by combining blind docking with k-means clustering. The interaction profile, key binding residues, and considerable interaction were elucidated for rubraxanthone binding to both Mpro sites. Integrated LB-PaCS-MD/FMO provided a more reasonable complex structure for ligand binding at the SARS-CoV-2 Mpro active site, which is vital for discovering and designing antiviral drugs.

show abstract

Section: Introductionmentioning

confidence: 99%

Promising SARS-CoV-2 main protease inhibitor ligand-binding modes evaluated using LB-PaCS-MD/FMO

Hengphasatporn

Harada

Wilasluck

et al. 2022

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Meanwhile, studied by Yuanita et al. (2019, 2021) found that adding a chloro substituent to hydroxyxanthone derivatives enhanced anticancer activity against T47D and HeLa cancer cells, and the addition of a bromo substituent improved efficacy against P388 cancer cells [12,13] …”

Section: Introductionmentioning

confidence: 99%

“…Yuanita, et al. in 2021 succeeded in conducting the bromination reaction in hydroxyxanthone derivatives using Br 2 in acetic acid [13] …”

Section: Introductionmentioning

confidence: 99%

In silico Approach for Design, Synthesis and Biological Evaluation of Tioxanthone Derivatives as Potential Anticancer Agents

Hermawan,

Jumina,

Pranowo

et al. 2024

ChemistrySelect

View full text Add to dashboard Cite

The investigation of thioxanthones involved molecular docking, molecular dynamics simulation, synthesis, and evaluation of their potential as anticancer agents. Molecular docking analyses indicated that 2,4‐dichloro‐1,3‐dihydroxythioxanthone and 2,4‐dibromo‐1,3‐dihydroxythioxanthone had lower binding energies and 4‐bromo‐1,3‐dihydroxythioxanthone had the similar binding energy compared to erlotinib. In 50 ns molecular dynamics simulation, 2,4‐dichloro‐1,3‐dihydroxythioxanthone and 2,4‐dibromo‐1,3‐dihydroxythioxanthone complex exhibited more stability than 4‐bromo‐1,3‐dihydroxythioxanthone and erlotinib, while it had similar stability with doxorubicin. These compounds comply the Lipinski's rule parameters and the minimum required parameters of ADMET. The evaluated anticancer activity of 2,4‐dichloro‐1,3‐dihydroxythioxanthone and 2,4‐dibromo‐1,3‐dihydroxythioxanthone revealed them inactive against cervical cancer (HeLa) and colorectal cancer (WiDr) with IC50 more than 100 μM, however was moderate activity toward breast cancer (T47D) and lung cancer (A549). The selectivity index (SI) values of those compounds (7.71–148.4) passed the parameter SI. Based on these findings, 2,4‐dibromo‐1,3‐dihydroxythioxanthone was the most promising anticancer candidate for T47D cancer cell.

show abstract

“…QSPR models are mathematical models relating chemical structure to various physicochemical and physical properties. Many research studies have been conducted in this area in recent years [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26]. Numerous published QSAR and QSPR models include lipophilicity parameters obtained by thin-layer chromatography and highperformance liquid chromatography in a reversed phase system, i.e., RP-TLC or RP-HPLC as R MW and logk w values, respectively or using computational approaches in the form of logP [27][28][29][30][31][32][33].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of the Usefulness of Topological Indices for Predicting Selected Physicochemical Properties of Bioactive Substances with Anti-Androgenic and Hypouricemic Activity

2023

View full text Add to dashboard Cite

Due to the observed increase in the importance of computational methods in determining selected physicochemical parameters of biologically active compounds that are key to understanding their ADME/T profile, such as lipophilicity, there is a great need to work on accurate and precise in silico models based on some structural descriptors, such as topological indices for predicting lipophilicity of certain anti-androgenic and hypouricemic agents and their derivatives, for which the experimental lipophilicity parameter is not accurately described in the available literature, e.g., febuxostat, oxypurinol, ailanthone, abiraterone and teriflunomide. Therefore, the following topological indices were accurately calculated in this paper: Gutman (M, Mν), Randić (0χ, 1χ, 0χν, 1χν), Wiener (W), Rouvray–Crafford (R) and Pyka (A, 0B, 1B) for the selected anti-androgenic drugs (abiraterone, bicalutamide, flutamide, nilutamide, leflunomide, teriflunomide, ailanthone) and some hypouricemic compounds (allopurinol, oxypurinol, febuxostat). Linear regression analysis was used to create simple linear correlations between the newly calculated topological indices and some physicochemical parameters, including lipophilicity descriptors of the tested compounds (previously obtained by TLC and theoretical methods). Our studies confirmed the usefulness of the obtained linear regression equations based on topological indices to predict ADME/T important parameters, such as lipophilicity descriptors of tested compounds with anti-androgenic and hypouricemic effects. The proposed calculation method based on topological indices is fast, easy to use and avoids valuable and lengthy laboratory experiments required in the case of experimental ADME/T studies.

show abstract

Molecular Docking of Xanthone Derivatives as Therapeutic Agent for Covid-19

Cited by 5 publications

References 0 publications

Promising SARS-CoV-2 main protease inhibitor ligand-binding modes evaluated using LB-PaCS-MD/FMO

Promising SARS-CoV-2 main protease inhibitor ligand-binding modes evaluated using LB-PaCS-MD/FMO

In silico Approach for Design, Synthesis and Biological Evaluation of Tioxanthone Derivatives as Potential Anticancer Agents

Evaluation of the Usefulness of Topological Indices for Predicting Selected Physicochemical Properties of Bioactive Substances with Anti-Androgenic and Hypouricemic Activity

Contact Info

Product

Resources

About