COMPARATIVE PHARMACOINFORMATIC ANALYSIS OF PHYSICOCHEMICAL PROPERTIES AND DRUG-LIKENESS IN DRD2- AND HDAC1-TARGETING COMPOUNDS
DOI:
https://doi.org/10.65327/bp.v12i2.2537Keywords:
DRD2, HDAC1, pharmacoinformatic, physicochemical properties, drug-likenessAbstract
A pharmacoinformatic approach was used to comparatively analyse the physicochemical and drug-likeness properties of the bioactive compounds that modulate the dopamine D2 receptor (DRD2) and histone deacetylase 1 (HDAC1). 1,331 compounds (1,273 DRD2-targeting and 58 HDAC1-targeting) were analysed. Descriptive statistics, Mann–Whitney U tests (with false discovery rate correction), Spearman correlation, Lipinski Rule-of-Five and principal component analysis (PCA) were used in conjunction with hierarchical clustering to analyse molecular weight, LogP, hydrogen-bond acceptors (HBA), hydrogen-bond donors (HBD), and topological polar surface area (TPSA). The differences in molecular weight, LogP, and HBA between the two target groups were not significant, while the differences in HBD and TPSA were significant. Compounds that target HDAC1 had a higher H-bond donor number and higher molecular polarity. However, overall drug-likeness rates were higher in most compounds of both classes, with higher rates in the DRD2 ligands. The first two PCs accounted for 81.5% of the total descriptor variance, and hierarchical cluster analysis indicated a partial grouping of the HDAC1 ligands according to their physicochemical properties. The overall results suggest that hydrogen-bond donor capacity and polar surface area are important physicochemical properties that separate the DRD2- and HDAC1-targeting molecules.
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Copyright (c) 2026 Dr. Humair Bin Md Omer, Dr. Abu Tayab Moin, Dr. Sharika Hossain
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