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Towards Antitumor Active trans ‐Platinum Compounds
Author(s) -
Aris Sheena M.,
Farrell Nicholas P.
Publication year - 2009
Publication title -
european journal of inorganic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.667
H-Index - 136
eISSN - 1099-0682
pISSN - 1434-1948
DOI - 10.1002/ejic.200801118
Subject(s) - chemistry , bifunctional , platinum , heteronuclear molecule , adduct , dna , cisplatin , stereochemistry , cytotoxicity , amine gas treating , combinatorial chemistry , zinc , organic chemistry , biochemistry , nuclear magnetic resonance spectroscopy , in vitro , catalysis , medicine , surgery , chemotherapy
Substitution of NH 3 by a range of amines in trans ‐[PtCl 2 (NH 3 ) 2 ] produces compounds with cytotoxicity significantly improved over the parent transplatin and in many cases equivalent to that of cisplatin. This microreview summarizes the chemistry and biology of trans ‐platinum compounds containing principally planar amines and succinctly reviews the current status of anticancer relevance of the trans ‐platinum geometry. The nature of bifunctional DNA adducts (intrastrand, interstrand) is remarkably dependent on the nature of the amine. Further, the stability of monofunctional adducts allows for competitive production of DNA–protein cross‐links and overall the results suggest that the trans ‐platinum chemotype may offer significant potential for design of selective DNA–protein cross‐linking agents. A subset of proteins known to bind to DNA modified by trans ‐platinum is that comprising zinc fingers – model studies show the potential for formation of heteronuclear thiolate‐bridged species as precedent for zinc displacement from the biomolecule.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)