Jump to main content
Jump to site search

Issue 23, 2010
Previous Article Next Article

Rationalization of the inhibition activity of structurally related organometallic compounds against the drug target cathepsin B by DFT

Author affiliations

Abstract

A series of organometallic compounds of general formula [(arene)M(PTA)nXm]Y (arene = η6-C10H14, η-C5Me5); M = Ru(II), Os(II), Rh(III) and Ir(III); X = Cl, mPTA; Y = OTf, PF6) have been screened for their cytotoxicity and ability to inhibit cathepsin B in vitro, in comparison to the antimetastatic compound NAMI-A. The Ru and Os analogues and NAMI-A showed similar enzyme inhibition properties (with IC50 values in the low μM range), whereas the Rh(III) and Ir(III) compounds were inactive. In order to build up a rational for the observed differences, DFT calculations of the metal complexes adducts with N-acetyl-L-cysteine-N′-methylamide, a mimic for the Cys residue in the cathepsin B active site, were performed to provide insights into binding thermodynamics in solution. Initial structure–activity relationships have been defined with the calculated binding energies of the M–S bonds correlating well with the observed inhibition properties of the compounds.

Graphical abstract: Rationalization of the inhibition activity of structurally related organometallic compounds against the drug target cathepsin B by DFT

Back to tab navigation

Supplementary files

Publication details

The article was received on 16 Feb 2010, accepted on 19 Apr 2010 and first published on 14 May 2010


Article type: Paper
DOI: 10.1039/C003218B
Citation: Dalton Trans., 2010,39, 5556-5563
  •   Request permissions

    Rationalization of the inhibition activity of structurally related organometallic compounds against the drug target cathepsin B by DFT

    A. Casini, F. Edafe, M. Erlandsson, L. Gonsalvi, A. Ciancetta, N. Re, A. Ienco, L. Messori, M. Peruzzini and P. J. Dyson, Dalton Trans., 2010, 39, 5556
    DOI: 10.1039/C003218B

Search articles by author

Spotlight

Advertisements