Binding interactions of Biginelli-type compounds with serum albumin and DNA

Abstract

Tetrahydropyrimidines (THPMs), synthesized via the classical Biginelli multicomponent reaction, represent a valuable class of heterocyclic compounds with diverse pharmacological potential. In our previous work, we reported the synthesis of a novel chlorine- containing tetrahydropyrimidine derivative with pronounced in vitro cytotoxicity against K562 leukemia cells. Building on these findings, the present study explores its interaction with DNA and human serum albumin (HSA) in order to gain insight into its potential mechanism of action and pharmacokinetic behavior. DNA binding was assessed by competitive studies with ethidium bromide (EB). The addition of compound A to the EB–DNA complex resulted in a concentration-dependent decrease of the fluorescence emission, indicating that compound A is capable of displacing EB. The calculated Stern–Volmer constant (KSV = 6.76 × 103 M−1) supports intercalation as the probable binding mode, although additional interactions such as groove binding cannot be excluded. The binding to HSA was examined by monitoring intrinsic fluorescence changes. Analysis using the Scatchard model provided a binding constant (Kb = 8.51 × 104 M−1), which is within the typical range for reversible ligand–protein complexes, and n ≈ 1 suggests the presence of a single dominant binding site for compound A on HSA. These findings imply that HSA may act as a potential carrier protein, affecting the distribution and bioavailability of this compound.