QSAR ANALYSIS OF HDAC6 INHIBITORS

Abstract

Histone deacetylase inhibitors are the most important class of drugs for the treatment of oncologies and other diseases due to their effect on cell growth, differentiation and apoptosis. Among the known eighteen histone deacetylases, Histone deacetylase 6 (HDAC6), which is involved in oncogenesis, cell survival, and cancer cell metastasis, is of high importance. Using 2D molecular descriptors RDKit, simplex descriptors, as well as methods of Random Forest (RF), Gradient Boosting (GBM), Support vectors (SVM), a number of adequate classi cation models of Quantitative Structure-Activity Relationship (QSAR) are proposed. For the models constructed using simplex descriptors, a structural interpretation was carried out, which made it possible to describe molecular fragments that increase and decrease the activity of HDAC6 inhibitors. The results of the structural interpretation were used for the rational molecular design of potential HDAC6 inhibitors, for which ADMET properties were also evaluated. Models built using 2D RDKit descriptors are freely available on the github platform (https://github.com/ovttiras/HDAC6-inhibitors).