Cisplatin structure

The polymeric nature may inhibit premature drug deactivation. Thus, cisplatin (structure 19.20), the most widely used anticancer drug, is converted into numerous inactive, but more toxic, platinum-containing compounds before it arrives at the targeted cancer cells. Placement of the active platinum-containing moiety into a polymer (structure 19.21) decreases this tendency to hydrolyze into these unwanted cisplatin compounds because of the greater hydrophobic character of the polymeric drug. 

Chemical Name Platinum, diamminedichloro-, (SP-4-2)-Common Name Cisplatin Structural Formula ... 

Structure, recognition, and processing of cisplatin-DNA adducts 99CRV2467. 

Bis(dicyclohexylammonium) bis(2,6-pyridinedicarboxylato)dibutylstannate is concluded to have sevenfold coordination at the Sn on the basis of its Sn CP/ MAS NMR chemical shift ((5 = —424.9 ppm). The assignment has been corroborated by crystal structure determination of its monohydrate, in which the Sn atom has frflMS-C2SnN04 PBP geometry (Sn-C = 204.0,206.7pm, C-Sn-C = 168.9°). One 2,6-pyiidinedicarboxylato group chelates to the Sn atom (Sn-O = 223.4,226.0 pm Sn-N = 227.9 pm), whereas the other binds through only one carboxyl end (Sn-O = 241.6, 244.1pm). The anhydrous compound displays higher in vitro antitumor activity than those of cisplatin and carboplatin (Table 7). ... 

Stein and co-workers have reported the structure of an unusual tetranuclear platinum(II) complex possessing both ammine and carbonato ligands.325 During a study of the reaction of cisplatin with Ag+, followed by the addition of 2 -deoxyuridine to afford platinum blue -like products from aqueous solution (pH < 2), a colorless minor product was isolated from the reaction mixture. X-ray crystallography confirmed that the product was a cyclo tetra-cation... 

Carloni, P., W. Andreoni, J. Hutter, A. Curioni, P. Gianozzi, and M. Parrinello. 1995. Structure and bonding in cisplatin and other Pt(H) complexes. Chem. Phys. Lett. 234,50. 

The earliest structure-activity relationships indicated that the transplatinum geometry is inactive— significantly higher doses must be given before any therapeutic effect is seen. In 1991, it was reported that alteration of amine structure and the introduction of sterically hindered amines produced cytotoxicity similar to that of cisplatin.162 The first examples used planar amines and a variety of tra s-[PtCl2(L)(L )] compounds have been synthesized and evaluated ((21)-(26), Figure 12).163... 

In the case of complexes such as (21) and (23) which have an extended planar ligand, a significantly higher proportion of interstrand cross-links in DNA is formed in comparison to either cis- or trans-platin.172 The steric effects of these planar ligands result in the formation of structurally unique 1,2-interstrand cross-links like those formed by cisplatin, a unique example of how steric effects may alter a nonactive lesion into an active one (Figure 13).173,174 Model studies predicted this outcome by preparation of the monofunctional models trans-[PtCl(9-ethylguanine) (NH3)(quinoline)] and comparison of substitution rates of the Pt—Cl bond by G or C mononucleotides.175 176 Interestingly, the iminoether compound (25) appears to form predominantly monofunctional adducts with DNA.177... 

Farrell, N. P. Qu, Y. Bierbach, U. Valsecchi, M. Menta, E. Structure-activity Relationships within Di- and Trinuclear Platinum Phase I Clinical Agents In Cisplatin Chemistry and Biochemistry of a Leading Anticancer Drug Lippert, B., Ed. Verlag, 1999, pp 479 196. 

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