A mechanism – based perspective on the interplay of new drug candidate with biomolecules

Abstract

This research deals with the synthesis and analysis of a novel Pd(II) compound, [Pd(dach)(SA)], featuring 1,2-diaminocyclohexane (dach) and salicylic acid (SA). The compound's structure was refined and its electronic properties including HOMO-LUMO energies, molecular electrostatic potential and natural bond analysis were calculated using B3LYP functional of DFT. Biologically, the compound demonstrated significant antitumor efficacy against the K562 leukemia cell line (IC50 = 37 μM). In-silico methods predicted the favorable characteristics and low risks of new compound. Interactions with DNA and serum albumin were explored using both experimental and computational techniques, revealing that the compound binds through hydrogen bonds and van der Waals forces having Kb,DNA = 1.7 × 105, ΔG°DNA = - 7.32 kcal/mol, Kb,BSA = 1.25 × 106 and ΔG°BSA = - 8.36 kcal/mol, as indicated by fluorescence spectroscopy. UV–Vis spectroscopy showed a reduction in the absorption spectra of both DNA and BSA upon interaction. DNA binding affinity was confirmed via gel electrophoresis and viscosity measurements. Molecular docking suggested the groove binding with DNA, and site I of BSA, primarily through hydrogen binding. The stability and conformational changes of these interactions over the time were affirmed by molecular dynamics simulations and QM/MM calculations. These comprehensive studies underscore the potential of [Pd(dach)(SA)] complex as a candidate for cancer therapy, highlighting its strong binding interactions with crucial biomolecules.