Molecular docking and QSPR of 5-O-acetylpinostrobin derivatives that inhibit ERα as breast cancer drug candidates

The development of new breast cancer drugs is carried out through Computer-Aided Drug Design. Molecular docking and the Quantitative-Structure Properties Relationship (QSPR) as a step to obtain more effective compounds, selective, and the most influential physicochemical parameters through structural modification. Structural modification through the addition of acetyl groups caused changes in the biological activity of the compound. The research aimed to discover breast cancer drug prediction and its relationship with QSPR 5-O-acetylpinostrobin derivatives. The anti-breast cancer prediction used AutoDock Tools with the ERα type (PDB: 6V87). The selected parameters include free energy binding and inhibition constants. The physicochemical properties and excretion parameters were determined via online pkCSM and SwissADME. The relationship between physicochemical properties and total clearance was determined based on the QSPR equation with SPSS. The results of molecular docking showed five compounds with free energy binding and minimum inhibition constant values, namely P1, P2, P3, P4, and P5, with free energy binding values of -7.86, -7.77, -7.57, -7.31, and -6.96 kcal/mol and inhibition constant values of 1.73, 2.02, 2.82, 4.37, and 7.88 mM, respectively. The best QSPR equation was (1/CLtot) = 0.130*nRB - 0.034*MR + 0.366*Log P + 1.534 (n = 20, r = 0.761, SE = 0.579, F = 7.331, .sig = 0.003). An increase in nRB and Log P values and a decrease in MR values affect the increase in total clearance. Based on the results of the study, the five 5-O-acetylpinostrobin derivative compounds have the potential to be synthesized and tested further in vitro.