Dinuclear palladium(II) complexes containing two monofunctional [Pd(en)(pyridine)Cl]+ units bridged by Se or S. Synthesis, characterization, cytotoxicity and kinetic studies of DNA-binding

J Inorg Biochem. 1998 Jul;70(3-4):219-26. doi: 10.1016/s0162-0134(98)10019-3.

Abstract

Two novel dinuclear palladium(II) complexes, ¿[Pd(en)Cl]2(bpse)¿(NO3)2 (1) and ¿[Pd(en)Cl]2 (bpsu)¿(NO3)2 (2), (where en is ethylenediamine; bpse is bis(3-methyl-4-pyridyl) selenide; bpsu is bis(3-methyl-4-pyridyl) sulfide) have been synthesized. The complexes have been characterized by elemental analysis, IR, 1H NMR, and 13C NMR. They have been assayed for antitumor activity in vitro against the mice leukemia L1210 and the human coloadenocarcinoma HCT8 cell lines. The results show that compound 1 has a lower I.D.50 value against the two cancer cell lines as compared to compound 2; the compounds also shows a lower I.D.50 value than cisplatin against the HCT8 cell line, but a higher I.D.50 value than cisplatin against the L1210 cell line. Binding studies indicate that compound 1 possibly interacts with DNA by a nonintercalative mode. Kinetics of binding of the two compounds to DNA are firstly studied using ethidium bromide as a fluorescence probe with stopped-flow spectrophotometer under pseudo-first-order condition. The stronger binding of two steps in the process of the compounds interacting with DNA are observed, and the Kobs and Ea of binding of the two steps (where Kobs is the observed pseudo-first-order rate constant, Ea is the observed energy of activation) are obtained.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology*
  • Cisplatin / pharmacology
  • DNA / metabolism*
  • Drug Screening Assays, Antitumor
  • Humans
  • Kinetics
  • Magnetic Resonance Spectroscopy
  • Mice
  • Molecular Structure
  • Organometallic Compounds / chemistry*
  • Organometallic Compounds / metabolism
  • Organometallic Compounds / pharmacology*
  • Organoselenium Compounds / chemistry*
  • Organoselenium Compounds / metabolism
  • Organoselenium Compounds / pharmacology*
  • Palladium / chemistry
  • Pyridines / chemistry*
  • Pyridines / metabolism
  • Pyridines / pharmacology*
  • Selenium / chemistry
  • Sulfur / chemistry

Substances

  • Antineoplastic Agents
  • Organometallic Compounds
  • Organoselenium Compounds
  • Pyridines
  • dichloro(ethylenediamine)palladium(II)bis(3-methyl-4-pyridyl)selenide
  • dichloro(ethylenediamine-)palladium(II)bis(3-methyl-4-pyridyl)sulfide
  • Palladium
  • Sulfur
  • DNA
  • Selenium
  • Cisplatin