Synthesis, conformational studies, and investigations on the estrogen receptor binding of [R/S-1-(2,6-dichloro-4-hydroxyphenyl)ethylenediamine]platinum(II) complexes

Arch Pharm (Weinheim). 2001 Mar;334(3):93-100. doi: 10.1002/1521-4184(200103)334:3<93::aid-ardp93>3.0.co;2-2.

Abstract

The syntheses, conformational studies, and investigations on the estrogen receptor binding of [R/S-1-(2,6-dichloro-4-hydroxyphenyl)ethylenediamine]platinum(II) complexes (1-PtL2, 2L = leaving groups) are described. A Strecker synthesis using the 2,6-dichloro-4-methoxybenzaldehyde, NaCN, and NH4Cl afforded the cyanoamine 1b, which was subsequently reduced with LiAlH4 to give the R/S-1-(2,6-dichloro-4-methoxyphenyl)ethylenediamine 1a. Ether cleavage with BBr3 yielded R/S-1-(2,6-dichloro-4-hydroxyphenyl)ethylenediamine 1 which was coordinated to platinum(II) by use of K2PtCl4 (1-PtCl2) and K2PtI4 (1-PtI2), respectively. Reaction of 1-PtI2 with Ag2SO4 and coordination of tartronic acid led to the [R/S-1-(2,6-dichloro-4- hydroxyphenyl)ethylenediamine][hydroxymalonato]platinum(II) complex (1-Pt(MalOH)). The spatial structure of 1 and its complexes was evaluated by spectroscopic and molecular modeling methods. In solution the complexes adopt a structure very similar to estradiol. However, the in vitro and in vivo tests for the compounds indicated neither affinity to the estrogen receptor nor estrogenic properties.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Estrogens / metabolism
  • Humans
  • Luciferases / metabolism
  • Molecular Conformation
  • Organoplatinum Compounds / chemical synthesis*
  • Organoplatinum Compounds / pharmacology*
  • Receptors, Estrogen / drug effects*

Substances

  • Estrogens
  • Organoplatinum Compounds
  • Receptors, Estrogen
  • Luciferases