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.