A Computational Approach to Investigate the HDAC6 and HDAC10 Binding Propensity of Psidium guajava-derived Compounds as Potential Anticancer Agents
| Autor: | Kayode Ezekiel Adewole, Ahmed Adebayo Ishola |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Psidium
Sequence Homology Amino Acid Plant Extracts medicine.drug_class Histone deacetylase inhibitor Histone Deacetylase 6 Histone Deacetylases Histone Deacetylase Inhibitors Molecular Docking Simulation chemistry.chemical_compound chemistry Biochemistry Catalytic Domain Neoplasms Betulinic acid Drug Discovery medicine Lipinski's rule of five Humans Histone deacetylase Apicidin Oleanolic acid Protein Binding ADME Discovery Studio |
| Zdroj: | Current Drug Discovery Technologies. 18:423-436 |
| ISSN: | 1570-1638 |
| Popis: | Background: Different parts of Psidium guajava are consumed as food and used for medicinal purposes around the world. Although studies have reported their antiproliferative effects via different biochemical mechanisms, their modulatory effects on epigenetic modification of DNA molecules via histone deacetylases (HDACs) are largely unknown. Objective: This study was carried out to investigate the histone deacetylase 6 (HDAC6) and histone deacetylase 10 (HDAC10) binding propensity of guava-derived compounds, using in silico methods, in other to identify compounds with HDAC inhibitory potentials. Methods: Fifty-nine guava-derived compounds and apicidin, a standard HDAC inhibitor, were docked with HDAC6 and HDAC10 using AutodockVina after modeling (SWISS-MODEL server) and validating (ERRAT and VERIFY-3D) the structure of HDAC10. Molecular interactions between the ligands and the HDACs were viewed with Discovery Studio Visualizer. Prediction of binding sites, surface structural pockets, active sites, area, shape and volume of every pocket and internal cavities of proteins was done using Computed Atlas of Surface Topography of proteins (CASTp) server, while absorption, distribution, metabolism, and excretion (ADME) study of notable compounds was done using Swiss online ADME web tool. Results: 2α-hydroxyursolic acid, asiatic acid, betulinic acid, crategolic acid, guajadial A and B, guavacoumaric acid, guavanoic acid, ilelatifol D, isoneriucoumaric acid, jacoumaric acid, oleanolic acid, psiguadial A, B, and C demonstrated maximum interaction with the selected HDACs. ADME studies revealed that although isoneriucoumaric and jacoumaric acid ranked very high as HDAC inhibitors, they both violated the Lipinski’s rule of 5. Conclusion: This study identified 13 drugable guava-derived compounds that can be enlisted for further studies as potential HDAC6 and HDAC10 inhibitors. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|