In-silico Prediction of Binding Affinities and Pharmacokinetic Parameters of Indoline-2-one Derivatives as Anticancer HDAC Inhibitors

The present work explores the molecular docking and pharmacokinetic features of indoline-2-one derivatives as potential anticancer agents by targeting histone deacetylase enzyme (HDAC1) which is the crucial element in tumor progression. Docking studies on the derivatives were performed based on histone deacetylase enzyme crystal structure (PDB ID: 1C3S) comparing with reference inhibitor vorinostat to ascertain inhibitory activity. Docking outcomes demonstrated that the fitness scores of all analogs are superior to those of vorinostat. The binding types were stabilized mainly by hydrogen bond, hydrophobic contact and coordination with the zinc ion in the active site of enzyme, showing good complementarity and certain inhibitory effect. Pharmacokinetics screening via the Swiss ADME (absorption, distribution, metabolism, and excretion) platform revealed that these compounds complied with the Lipinski’s rule for drug likeness, and had favorable physicochemical properties (good lipophilicity, suitable topological polar surface area values as well as good gastrointestinal absorption). The indoline-2-one derivatives did not interact with P-glycoprotein and presented a good oral bioavailability. These results indicate that these compounds exhibit predicted inhibitory potential toward the histone deacetylase enzyme, supported by favorable docking scores and pharmacokinetic properties and can be further optimized for anticancer drug research.