Biological Activity of Two Anticancer Pt Complexes with a Cyclohexylglycine Ligand against a Colon Cancer Cell Line: Theoretical and Experimental Study

Because of their
extraordinary ability to disrupt the natural structure
of nucleic acids, metal complexes could be used in cancer therapy.
In this study, cyclohexylglycine (HL) as a ligand and
two new Pt complexes, [Pt(NH3)2(L)]NO3 (1) and [Pt(bipy)(L)]NO3 (2), were synthesized and characterized by elemental analysis, LC-MS,
UV–vis spectrometry, FT-IR, 1H NMR spectroscopy, 13C NMR spectroscopy, 195Pt NMR spectroscopy, HPLC
analysis, and single-crystal X-ray diffraction. Complex 2 crystallized in the orthorhombic Pbca space group,
and density functional theory (DFT) was used to describe its structural
parameters were described in detail. These complexes can be classified
as oral medications and drug-like molecules based on a comparison
of their absorption, distribution, metabolism, and excretion assessment.
Quantum chemical descriptors (QCDs) were determined using DFT calculations
to predict the tendency of DNA to approach these complexes. During
the determination of the function of the metallodrug in DNA binding,
the fluorescence data indicated that static quenching took place for
all ligands and complexes with higher DNA binding affinity. CD and
isothermal absorption studies indicate the presence of electrostatic
and groove binding for the amine derivative and that DNA binds with
the bipy moiety via groove binding. Furthermore, the interaction modes
were determined using molecular docking to investigate the binding
of these compounds with the target DNA molecule. According to docking
investigations, binding energies of −5.7, −11.56, and
−10.00 kcal/mol for HL and complexes 1 and 2, respectively, indicate partially electrostatic
and groove binding. The anticancer activities of the Pt(II) complexes
were tested against the HCT116 human colon cancer cell line, with
IC50 values of 35.51 and 51.33 μM for 1 and 2, respectively, after 72 h. These values show
that the inhibitory effect of complex 1 was better than
those of 2 and carboplatin (IC50 = 51.94 μM).