Applied Chemical Engineering

Molecular docking and molecular dynamic of new thioguanine derivatives as histone deacetylase inhibitors

Mustafa M. Mukhlif

Department of Pharmaceutical Chemistry, College of Pharmacy, Al-Bayan University, 10011, Iraq

Ameer H. Alwash

Department of Pharmaceutical Chemistry, College of Pharmacy, Al-Bayan University, 10011, Iraq

Saraa M. Harbi

Department of Pharmaceutical Chemistry, College of Pharmacy, Al-Bayan University, 10011, Iraq

https://orcid.org/0009-0003-1689-5611

Shymaa A. Husein

Department of Pharmacy, Al-Nukhba University Collage, 10011, Iraq

Mohammed Khalid Abbood

Department of Clinical Pharmacy, College of Pharmacy, Al-Bayan University, 10011, Iraq

Hind A. Yaseen

Ibn Sina University of Medical and Pharmaceutical Sciences, 10011, Iraq

DOI: https://doi.org/10.59429/ace.v8i4.5748

Keywords: histone deacetylase; thioguanine; purine analogs; molecular docking; molecular dynamic.

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Abstract

Histone deacetylase inhibitors (HDAC-I) comprise structurally diverse molecules that are a group of targeted anticancer agents. Thioguanine is Purine derivatives used for acute myeloid leukemia treatment. A five new proposed analogs of thioguanine was investigated through molecular docking simulation to assess their binding affinity and therapeutic activity. Molecular dynamic (MD) modeling was conducted for 100 nanoseconds (ns) to investigate the molecular stability of the proposed compounds with the best docking results with histone deacetylase-2 (HDAC-2) and histone deacetylase-8 (HDAC-8) binding pocket. Root mean square deviation (RMSDs) for the ligands and complexes concerning their initial locations inside the active site has been reported and examined. 

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