Anticancer activity of new imidazole derivative of 1R,2R-diaminocyclohexane palladium and platinum complexes as DNA fluorescent probes

Abstract

The aim of this study was synthesis of two new water-soluble fluorescent palladium and platinum complexes with formulas of [Pt(DACH)(FIP)](NO₃)₂ and [Pd(DACH)(FIP)](NO₃)₂, respectively, where FIP is 2-(furan-2-yl)-1H-imidazo[4,5-f][1,10] phenanthroline and DACH is 1R,2R-diaminocyclohexane. Fluorescence spectroscopy, circular dichroism (CD), thermal denaturation measurement, ionic strength, and kinetic study displayed groove binding of Pt complex on DNA, while due to binding of Pd complex, B form of DNA convert to Z form. Due to electrostatic interaction of Pd complex with DNA, the DNA form is converted and it provides enough space for Pd complex to insert between base stacking of DNA. UV–vis study shows two complexes could denature the DNA at low concentrations in exothermic process and Pt complex is more active than Pd complex. Finally, the anticancer and growth inhibitory activities of synthesized complexes were investigated against human colon cancer cell line HCT116 after incubation time of 24 h using MTT assay and higher activity was observed for the platinum complex. Interaction of the two metal derivative complexes was studied by molecular docking and molecular dynamics simulation. The results showed that Pt complexes have higher negative docking energy and higher tendency for interaction with DNA, and exert more structural change on DNA.

Keywords:

• Imidazole derivative
• DNA binding
• Platinum and palladium complexes
• Fluorescent complex
• Molecular dynamics and docking

List of abbreviations:

• CT-DNA: calf tymus DNA
• EB: ethidium bromide
• FIP: 2-(furan-2-yl)-1H-imidazo[4,5-f][1,10]phenanthroline
• (R,R-DACH): (1R,2R)-(−)-1,2-Diaminocyclohexane
• CD: circular dichroism

Acknowledgment

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.