Computational Insights into Natural Antischistosomal Metabolites as SmHDAC8 Inhibitors: Molecular Docking, ADMET Profiling, and Molecular Dynamics Simulation

Alzain, Abdulrahim A.; Mukhtar, Rua M.; Abdelmoniem, Nihal; Elbadwi, Fatima A.; Hussien, Amira; Garelnabi, Elrashied A. E.; Osman, Wadah; Sherif, Asmaa E.; Khedr, Amgad I. M.; Ghazawi, Kholoud F.; Samman, Waad A.; Ibrahim, Sabrin R. M.; Mohamed, Gamal A.; Ashour, Ahmed

doi:10.3390/metabo13050658

Open AccessArticle

Computational Insights into Natural Antischistosomal Metabolites as SmHDAC8 Inhibitors: Molecular Docking, ADMET Profiling, and Molecular Dynamics Simulation

by

Abdulrahim A. Alzain

^1,*,†

,

Rua M. Mukhtar

^1,†,

Nihal Abdelmoniem

^1,†,

Fatima A. Elbadwi

¹

,

Amira Hussien

²,

Elrashied A. E. Garelnabi

³,

Wadah Osman

^4,5,

Asmaa E. Sherif

^4,6,

Amgad I. M. Khedr

⁷

,

Kholoud F. Ghazawi

⁸,

Waad A. Samman

⁹,

Sabrin R. M. Ibrahim

^10,11,

Gamal A. Mohamed

¹² and

Ahmed Ashour

^4,6

¹

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Gezira, Wad Madani 21111, Sudan

²

Department of Pharmacology, Faculty of Pharmacy, University of Gezira, Wad Madani 21111, Sudan

³

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Khartoum, Al-Qasr Ave, Khartoum 11111, Sudan

⁴

Department of Pharmacognosy, Faculty of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia

⁵

Department of Pharmacognosy, Faculty of Pharmacy, University of Khartoum, Al-Qasr Ave, Khartoum 11111, Sudan

⁶

Department of Pharmacognosy, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt

⁷

Department of Pharmacognosy, Faculty of Pharmacy, Port Said University, Port Said 42526, Egypt

⁸

Clinical Pharmacy Department, College of Pharmacy, Umm Al-Qura University, Makkah 24382, Saudi Arabia

⁹

Department of Pharmacology and Toxicology, College of Pharmacy, Taibah University, Al-Madinah Al-Munawwarah 30078, Saudi Arabia

¹⁰

Preparatory Year Program, Department of Chemistry, Batterjee Medical College, Jeddah 21442, Saudi Arabia

¹¹

Department of Pharmacognosy, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt

¹²

Department of Natural Products and Alternative Medicine, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia

Show full affiliation list

Hide full affiliation list

^*

Author to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Metabolites 2023, 13(5), 658; https://doi.org/10.3390/metabo13050658

Submission received: 16 April 2023 / Revised: 12 May 2023 / Accepted: 14 May 2023 / Published: 15 May 2023

(This article belongs to the Special Issue Extraction, Characterization, Chemical Composition and Biological Activity of Natural Metabolites)

Download

Browse Figures

Versions Notes

Abstract

Schistosomiasis is a neglected tropical disease with a significant socioeconomic impact. It is caused by several species of blood trematodes from the genus Schistosoma, with S. mansoni being the most prevalent. Praziquantel (PZQ) is the only drug available for treatment, but it is vulnerable to drug resistance and ineffective in the juvenile stage. Therefore, identifying new treatments is crucial. SmHDAC8 is a promising therapeutic target, and a new allosteric site was discovered, providing the opportunity for the identification of a new class of inhibitors. In this study, molecular docking was used to screen 13,257 phytochemicals from 80 Saudi medicinal plants for inhibitory activity on the SmHDAC8 allosteric site. Nine compounds with better docking scores than the reference were identified, and four of them (LTS0233470, LTS0020703, LTS0033093, and LTS0028823) exhibited promising results in ADMET analysis and molecular dynamics simulation. These compounds should be further explored experimentally as potential allosteric inhibitors of SmHDAC8.

Keywords: schistosomiasis; SmHDAC8; allosteric; phytochemicals; molecular docking; molecular dynamics; drug discovery; health and wellbeing

Graphical Abstract

Share and Cite

MDPI and ACS Style

Alzain, A.A.; Mukhtar, R.M.; Abdelmoniem, N.; Elbadwi, F.A.; Hussien, A.; Garelnabi, E.A.E.; Osman, W.; Sherif, A.E.; Khedr, A.I.M.; Ghazawi, K.F.; et al. Computational Insights into Natural Antischistosomal Metabolites as SmHDAC8 Inhibitors: Molecular Docking, ADMET Profiling, and Molecular Dynamics Simulation. Metabolites 2023, 13, 658. https://doi.org/10.3390/metabo13050658

AMA Style

Alzain AA, Mukhtar RM, Abdelmoniem N, Elbadwi FA, Hussien A, Garelnabi EAE, Osman W, Sherif AE, Khedr AIM, Ghazawi KF, et al. Computational Insights into Natural Antischistosomal Metabolites as SmHDAC8 Inhibitors: Molecular Docking, ADMET Profiling, and Molecular Dynamics Simulation. Metabolites. 2023; 13(5):658. https://doi.org/10.3390/metabo13050658

Chicago/Turabian Style

Alzain, Abdulrahim A., Rua M. Mukhtar, Nihal Abdelmoniem, Fatima A. Elbadwi, Amira Hussien, Elrashied A. E. Garelnabi, Wadah Osman, Asmaa E. Sherif, Amgad I. M. Khedr, Kholoud F. Ghazawi, and et al. 2023. "Computational Insights into Natural Antischistosomal Metabolites as SmHDAC8 Inhibitors: Molecular Docking, ADMET Profiling, and Molecular Dynamics Simulation" Metabolites 13, no. 5: 658. https://doi.org/10.3390/metabo13050658

APA Style

Alzain, A. A., Mukhtar, R. M., Abdelmoniem, N., Elbadwi, F. A., Hussien, A., Garelnabi, E. A. E., Osman, W., Sherif, A. E., Khedr, A. I. M., Ghazawi, K. F., Samman, W. A., Ibrahim, S. R. M., Mohamed, G. A., & Ashour, A. (2023). Computational Insights into Natural Antischistosomal Metabolites as SmHDAC8 Inhibitors: Molecular Docking, ADMET Profiling, and Molecular Dynamics Simulation. Metabolites, 13(5), 658. https://doi.org/10.3390/metabo13050658

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Menu

Computational Insights into Natural Antischistosomal Metabolites as SmHDAC8 Inhibitors: Molecular Docking, ADMET Profiling, and Molecular Dynamics Simulation

Abstract

Share and Cite

Article Metrics

Article Access Statistics

Further Information

Guidelines

MDPI Initiatives

Follow MDPI