Improving activity of anticancer oxalipalladium analog by the modification of oxalate group with isopentylglycine

Abstract

In this article, we describe the influence of structure on biological behavior of amino acid-Pd complex and compare it with oxalipalladium. A new water-soluble oxalipalladium analog with formula of [Pd(DACH)(isopentylgly)](NO₃), where DACH is 1R,2R-diaminocyclohexane, has been synthesized and characterized by elemental analysis, conductivity measurements, IR, UV–Vis, and ¹H NMR spectroscopies. The interactions of oxalipalladium and its amino acid derivative with highly polymerized calf-thymus DNA have been extensively studied by spectroscopic methods. The high binding constants of oxalipalladium (0.38 × 10⁴ M⁻¹) and new amino acid-Pd complex (0.65 × 10⁴ M⁻¹) were determined using absorption measurements. Also circular dichroism (CD) studies show that Pd complex causes more disturbances on DNA structure rather than oxalipalladium. The experimental results proposed that [Pd(DACH)(isopentylgly)](NO₃) is bound to DNA by groove-binding mode as well as partially covalent interaction, while oxalate analog binds covalently to DNA after hydrolysis. Interaction of the two metal derivative complexes was studied by molecular docking simulation. The results showed that amino acid-Pd complex has higher negative docking energy and higher tendency for interaction with DNA, and exert more structural change on DNA. Finally, the anticancer and growth inhibitory activities of synthesized complexes were investigated against human colon cancer cell line of HCT116 after 24  h incubation time using MTT assay. Results show that the complex [Pd(DACH)(isopentylgly)](NO₃) showed enhanced anticancer and growth inhibitory activities against human colon can cell line HCT116.

Keywords:

• Cytotoxicity
• DNA binding
• glycine derivative
• oxalipalladium
• molecular docking

Acknowledgements

The authors gratefully acknowledge the financial support of this work by the Chemistry & Chemical Engineering Research Center of Iran. We express our gratitude to Shahrood University of Technology and University of Tehran.