Repository logo

Infoscience

  • English
  • French
Log In
Logo EPFL, École polytechnique fédérale de Lausanne

Infoscience

  • English
  • French
Log In
  1. Home
  2. Academic and Research Output
  3. Journal articles
  4. Rational design of organo-ruthenium anticancer compounds
 
research article

Rational design of organo-ruthenium anticancer compounds

Gossens, Christian  
•
Tavernelli, Ivano  
•
Rothlisberger, Ursula  
2005
CHIMIA

Organometallic ruthenium(II)-arene complexes are currently attracting increasing interest as anticancer compds. with the potential to overcome drawbacks of traditional drugs like cisplatin with respect to resistance, selectivity, and toxicity. Rational design of new potential pharmaceutical compds. requires a detailed understanding of structure-property relationships at an at. level. We performed in vacuo d. functional theory (DFT) calcns., classical MD, and mixed QM/MM Car-Parrinello MD explicit solvent simulations to rationalize the binding mode of two series of anticancer ruthenium(II) arene complexes to double-stranded DNA (dsDNA). Binding energies between the metal centers and the surrounding ligands as well as proton affinities were calcd. using DFT. Our results support a pH-dependent mechanism for the activity of the RAPTA [Ru(h6-arene)X2(pta)] (pta = 1,3,5-triaza-7-phosphatricyclo[3.3.1.1]decane) compds. Adducts of the bifunctional RAPTA and the monofunctional [Ru(h6-p-cymene)Xen]+ series of compds. with the DNA sequence d(CCTCTGGTCTCC)/d(GGAGACCAGAGG), where G* are guanosine bases that bind to the ruthenium compds. through their N(7) atom, have been investigated. The resulting binding sites were characterized in QM/MM mol. dynamics simulations showing that DNA can easily adapt to accommodate the ruthenium compds. [on SciFinder (R)]

  • Details
  • Metrics
Type
research article
DOI
10.2533/000942905777676795
Web of Science ID

WOS:000227933200006

Author(s)
Gossens, Christian  
Tavernelli, Ivano  
Rothlisberger, Ursula  
Date Issued

2005

Published in
CHIMIA
Volume

59

Issue

3

Start page

81

End page

84

Editorial or Peer reviewed

REVIEWED

Written at

EPFL

EPFL units
LCBC  
Available on Infoscience
February 27, 2006
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/226229
Logo EPFL, École polytechnique fédérale de Lausanne
  • Contact
  • infoscience@epfl.ch

  • Follow us on Facebook
  • Follow us on Instagram
  • Follow us on LinkedIn
  • Follow us on X
  • Follow us on Youtube
AccessibilityLegal noticePrivacy policyCookie settingsEnd User AgreementGet helpFeedback

Infoscience is a service managed and provided by the Library and IT Services of EPFL. © EPFL, tous droits réservés