Novel achiral titanocene anti-cancer drugs synthesised from bis-N,N-dimethylamino fulvene and lithiated heterocyclic compounds

Biometals. 2008 Apr;21(2):197-204. doi: 10.1007/s10534-007-9108-5. Epub 2007 Jul 31.

Abstract

From the carbolithiation of 6-bis-N,N-dimethylamino fulvene (3a) and different ortho-lithiated heterocycles (furan, thiophene and N-methylpyrrole), the corresponding lithium cyclopentadienide intermediate (4a-c) was formed. These three lithiated intermediates underwent a transmetallation reaction with TiCl(4) resulting in bis-N,N-dimethylamino-functionalised titanocenes 5a-c. When these titanocenes were tested against LLC-PK cells, the IC(50)-values obtained were of 240, and 270 microM for titanocenes 5b and 5c, respectively. The most cytotoxic titanocene in this paper, 5a with an IC(50)-value of 36 microM was found to be approximately six times less cytotoxic than its mono-N,N-dimethylamino substituted analogue Titanocene C (IC(50) = 5.5 microM) and almost ten times less cytotoxic than cisplatin, which showed an IC(50)-value of 3.3 microM, when tested on the LLC-PK cell line.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents* / chemical synthesis
  • Antineoplastic Agents* / chemistry
  • Antineoplastic Agents* / therapeutic use
  • Cell Line, Tumor
  • Cyclopentanes / chemistry*
  • Drug Evaluation, Preclinical
  • Heterocyclic Compounds / chemistry*
  • Humans
  • Inhibitory Concentration 50
  • Molecular Conformation
  • Molecular Structure
  • Neoplasms / drug therapy*
  • Organometallic Compounds* / chemical synthesis
  • Organometallic Compounds* / chemistry
  • Organometallic Compounds* / therapeutic use

Substances

  • Antineoplastic Agents
  • Cyclopentanes
  • Heterocyclic Compounds
  • Organometallic Compounds
  • titanocene
  • fulvene