Asymmetric transfer hydrogenation by synthetic catalysts in cancer cells

Research output: Contribution to journalArticlepeer-review

Authors

  • James P. C. Coverdale
  • Carlos Sanchez-cano
  • Guy J. Clarkson
  • Abraha Habtemariam
  • Martin Wills
  • Peter J. Sadler

Colleges, School and Institutes

Abstract

Catalytic anticancer metallodrugs active at low doses could minimize side-effects, introduce novel mechanisms of action that combat resistance and widen the spectrum of anticancer-drug activity. Here we use highly stable chiral half-sandwich organometallic Os(II) arene sulfonyl diamine complexes, [Os(arene)(TsDPEN)] (TsDPEN, N-(p-toluenesulfonyl)-1,2-diphenylethylenediamine), to achieve a highly enantioselective reduction of pyruvate, a key intermediate in metabolic pathways. Reduction is shown both in aqueous model systems and in human cancer cells, with non-toxic concentrations of sodium formate used as a hydride source. The catalytic mechanism generates selectivity towards ovarian cancer cells versus non-cancerous fibroblasts (both ovarian and lung), which are commonly used as models of healthy proliferating cells. The formate precursor N-formylmethionine was explored as an alternative to formate in PC3 prostate cancer cells, which are known to overexpress a deformylase enzyme. Transfer-hydrogenation catalysts that generate reductive stress in cancer cells offer a new approach to cancer therapy.

Details

Original languageEnglish
Pages (from-to)347-354
Number of pages8
JournalNature Chemistry
Volume10
Early online date8 Jan 2018
Publication statusPublished - 1 Mar 2018

Keywords

  • Biocatalysis, Bioinorganic chemistry