Development of Bimetallic Titanocene-Ruthenium-Arene Complexes As Anticancer Agents: Relationships between Structural and Biological Properties

Pelletier, F., Comte, V., Massard, A., Wenzel, M., Toulot, S., Richard, P., Picquet, M., Le Gendre, P., Zava, O., Edafe, F., Casini, A. & Dyson, P. J., 14-Oct-2010, In : Journal of Medicinal Chemistry. 53, 19, p. 6923-6933 11 p.

Research output: Contribution to journalArticleAcademicpeer-review

  • F. Pelletier
  • V. Comte
  • A. Massard
  • M. Wenzel
  • S. Toulot
  • P. Richard
  • M. Picquet
  • P. Le Gendre
  • O. Zava
  • F. Edafe
  • A. Casini
  • P.J. Dyson

A series of bimetallic titanium ruthenium complexes of general formula 1(eta(5)-C(5)H(5))(mu-eta(5):k(1)-C(5)H(4-)-(CR(2)) (CR(2))(n) PR'R '')TiCl(2)](eta(6)-p-cymene)RuCl(2)(n = 0,1.2 or 4; R = H or Me: R ' = H. Ph or Cy) have been synthesized. including two novel compounds as \'ell as two cationic derivatives of formula [(eta(5)-C(5)H(5))(mu-eta(5)):K(1)-C(5)H(4)(C(5)H(5))(n)PPh(2))TiCl(2)] [eta(6-)p-eymene)RuCl](BF(4)) (n = 0 or 2). The solid state structure of two of these compounds was also established by X-ray crystallography. The complexes showed a cytotoxic effect on human ovarian cancer cells and were markedly more active than their Ti or Ru monometallic analogues titanocene dichloride and RA PTA-C. respectively. Studies of cathcpsin 13 inhibition, an enzyme involved in cancer progression, showed that enzyme inhibition by the bimetallic complexes is influenced by the length of the alkyl chain in between the metal centers. Complementary ESI-MS studies provided evidence for binding of a Ru(11) fragment to proteins.

Original languageEnglish
Pages (from-to)6923-6933
Number of pages11
JournalJournal of Medicinal Chemistry
Issue number19
Publication statusPublished - 14-Oct-2010

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