• English
    • Türkçe
  • English 
    • English
    • Türkçe
  • Login
View Item 
  •   DSpace Home
  • Araştırma Çıktıları / Scopus
  • Araştırma Çıktıları / Scopus
  • View Item
  •   DSpace Home
  • Araştırma Çıktıları / Scopus
  • Araştırma Çıktıları / Scopus
  • View Item
JavaScript is disabled for your browser. Some features of this site may not work without it.

Discovery of novel isoform-selective histone deacetylases 5 and 9 inhibitors through combined ligand-based pharmacophore modeling, molecular mocking, and molecular dynamics simulations for cancer treatment

Thumbnail
View/Open
1-s2.0-S1093326321001066-main.pdf (8.661Mb)
Date
2021-07
Author
Elmezayen, Ammar D.
Al-Obaidi, Anas
Yelekçi, Kemal
Abstract
Class IIa histone deacetylases (HDACs) 5 and 9 play crucial roles in several human disorders such as cancer, making them important targets for drug design. Continuous research is pursed to overcome the cytotoxicity side effect that comes with the currently available broad-spectrum HDACs inhibitors. Herein, common features of active HDACs inhibitors in clinical trials and use have been calculated to generate the best pharmacophore hypothesis. Guner-Henry scoring system was used to validate the generated hypotheses. Hypo1 of HDAC5 and Hypo2 of HDAC9 exhibited the most statistically significance hypotheses. Compounds with fit value of 3 and more were examined by QuickVina 2 docking tool to calculate their binding affinity toward all class IIa HDACs. A total of 6 potential selective compounds were subjected to 100 molecular dynamics (MD) simulation to examine their binding modes. The free binding energy calculations were computed according to the MM-PBSA method. Proposed selective compounds displayed good stability with their targets and thus they may offer potent leads for the designing of HDAC5 and HDAC9 isoform selective inhibitors.

Source

Journal of Molecular Graphics and Modelling

Volume

106

URI

https://hdl.handle.net/20.500.12469/4041

Collections

  • Araştırma Çıktıları / Scopus [1565]
  • Araştırma Çıktıları / WOS [1518]

Keywords

HDAC5
HDAC9
MD simulation
MM-PBSA
Pharmacophore modeling

Share


DSpace software copyright © 2002-2015  DuraSpace
Contact Us | Send Feedback
Theme by 
@mire NV
 

 

Browse

All of DSpaceCommunities & CollectionsBy Issue DateBy AuthorsBy TitlesBy SubjectsBy TypesBy LanguagesBy DepartmentsBy PublishersBy KHAS AuthorsBy Access TypesThis CollectionBy Issue DateBy AuthorsBy TitlesBy SubjectsBy TypesBy LanguagesBy DepartmentsBy PublishersBy KHAS AuthorsBy Access Types

My Account

LoginRegister

Statistics

View Google Analytics Statistics

DSpace software copyright © 2002-2015  DuraSpace
Contact Us | Send Feedback
Theme by 
@mire NV