74790-01-5Relevant academic research and scientific papers
Chemical properties and antitumor activity of complexes of platinum containing substituted sulfoxides [PtCl(R′R″SO)(diamine)]NO3. Chirality and leaving group ability of sulfoxide affecting biological activity
Farrell, Nicholas,Kiley, Donna M.,Schmidt, Wendy,Hacker, Miles P.
, p. 397 - 403 (2008/10/08)
The preparation and antitumor activity in L1210 leukemia of a novel set of platinum complexes of formula [PtCl(R′R″SO)-(diam)]NO3 (diam = bidentate amine such as 1,2-diaminocyclohexane (dach) or 1,1-bis(aminomethyl)cyclohexane (damch) and R′R″SO = substituted sulfoxides such as dimethyl (Me2SO), methyl benzyl (MePhSO), methyl benzyl (MeBzSO), diphenyl (Ph2SO), and dibenzyl sulfoxide (Bz2SO)) is reported. The complexes are the first well-defined antitumor platinum complexes containing sulfur as ligand. The antitumor activity is dependent on both the nature of the amine and, especially the nature of the sulfoxide. In the case of asymmetric sulfoxides, such as methyl p-tolyl sulfoxide (MeTolSO), preparation of the optically pure forms shows a distinct effect of chirality of the sulfoxide ligand on the biological activity. The possible mechanisms of antitumor action are discussed. Studies on displacement of sulfoxide by Cl- and H2O show the order of lability to be Ph2SO > MePhSO > MeTolSO > Bz2SO > MeBzSO > Me2SO. The lability is also dependent on amine, with damch complexes being significantly more reactive than their dach analogues. The pseudo-first-order rate constants, which range over 2 orders of magnitude, preclude a simple loss of sulfoxide as a mechanism of antitumor activity. The complexes may act by binding to DNA with subsequent loss of sulfoxide ligand.
