Synthesis of Rare Earth Complexes With N-Pyrimidine Norcantharidin Acylamide Acid, DNA-Binding, and Antiproliferative Activity

Abstract

Three new rare earth complexes containing a ligand of N-pyrimidine norcantharidin acylamide acid, (HL = 3-pyrimidine carbamoyl-7-oxabicyclo[2.2.1] heptane-2-carboxylic acid, C₁₂H₁₃N₃O₄), were synthesized and characterized by elemental analysis, conductivity measurement, infrared spectroscopy and thermogravimetric analysis. The general chemical formula of these complexes was [RE(L)(NO₃)(H₂O)₂]NO₃·2H₂O, (RE = Eu(III) (1), Gd(III) (2), Ho(III) (3)). The analytic results indicated that the oxygen atoms are from the carbonyl, cyclic ether, and carboxylate groups of HL coordinated to RE(III), and there were also one nitrate and two waters participating in coordination. RE(III) and HL formed 1:1 chelate complexes and the suggested coordination number was eight. The interactions between the complexes and DNA have been investigates by means of fluorescence spectra, viscosity and agarose gel electrophoresis. The results suggest that the complexes can bind to DNA by partial intercalation. The complexes could quench the emission intensities of EB-DNA system significantly with Stern–Vollmer quenching constant K_sq of 4.8(1), 3.1(2), and 1.5(3), respectively. These complexes have been found to be able to cleave pBR322 plasmid DNA under physiological pH and temperature. The inhibition rates of complex (1) (IC₅₀ = 42.8 ± 2.5 μmol·L⁻¹) and complex (2) (IC₅₀ = 72.9 ± 7.9 μmol·L⁻¹) are much higher compared to that of HL (IC₅₀ = 84.2 ± 4.1 μmol·L⁻¹) against the SMMC7721 cell lines. The Eu(III) complex (1) seems to be well suited for further work aiming at developing new anticancer agents.

Keywords:

• norcantharidin
• pyrimidine
• acylamide acid
• rare earth complex
• DNA binding
• antiproliferative activity

Acknowledgements

The authors thank Institute of Zhejiang Academy of Medical Science for helping with antiproliferative activity test.

Additional information

Funding

Financial support, which is from the Natural Science Foundation of Zhejiang Province, China (Grant No. Y407301), is gratefully acknowledged.