Cisplatin properties

Hambley and co-workers have reported the synthesis, DNA cross-linking, and in vitro anticancer properties of a platinum(II) complex that was designed to bind the macromolecule in an interstrand rather than intrastrand manner,162 the latter being the dominant mode of DNA-binding by platinum anticancer drugs such as cisplatin. The complex [PtCl2(hpip)] ((46) ... 

Tornaghi, E., W. Andreoni, P. Carloni, J. Hutter, and M. Parrinello. 1995. Carboplatin versus cisplatin density functional approach to their molecular properties. Chem. Phys. Lett. 246, 469. 

SH-SY5Y neuroblastoma, cisplatin-sensitive A2780 and cispla-tin-resistant A2780cis human ovarian cancer cells was observed, but upon irradiation 7 strongly reduced the viability of the cancer cells (Fig. 8). In the A2780 cell line, the complex was 80x more toxic than cisplatin under identical conditions, and ca. 15 x more effective against the cisplatin-resistant A2780cis cell line (33). The trans diazido-Pt(IV) complex therefore has remarkable cytotoxic properties. 

The first report on the anticancer properties of ruthenium was published in 1976 when the Ru(III) compound /ac-[RuC13(NH3)3] (Fig. 11) was found to induce filamentous growth of Escherichia coli at concentrations comparable to those at which cisplatin generates similar effects (49). This Ru(III) complex and related compounds such as cis-[RuCl2(NH3)4]Cl illustrated the potential anticancer activity of ruthenium complexes, but insolubility prevented further pharmacological use. Since these initial studies, other Ru(III) complexes have been studied for potential anticancer activity, and two compounds, NAMI-A (50) and KP1019 (51), are currently undergoing clinical trials. Remarkably,... 

These compounds belong to a broad class of pharmacological agents possessing D2-dopamine blocking properties which are responsible for dystonic reactions. Prochlorperazine, the most widely used phenothiazine, was more effective than placebo but did not offer advantage over the cannabinoids or butyrophenones [123], It was less effective than metoclopramide against cisplatin [81]. 

Fumarase, inhibition by cisplatin, 37 195 Fumarate reductase cysteine distribution, 38 240-241 EPR, 47 452-456 ground-state properties, 47 23... 

Oxidative stress reduces the rate of cell proliferation, and that occurring during chemotherapy may interfere with the cytotoxic effects of antineoplastic drugs, which depend on rapid proliferation of cancer cells for optimal activity. Antioxidants detoxify ROS and may enhance the anticancer effects of chemotherapy. For some supplements, activities beyond their antioxidant properties, such as inhibition of topoisomerase II or protein tyrosine kinases, may also contribute. ROS cause or contribute to certain side effects that are common to many anticancer drugs, such as gastrointestinal toxicity and muagenesis. ROS also contribute to side effects that occur only with individual agents, such as doxorubicin-induced cardiotoxicity, cisplatin-induced nephrotoxicity, and bleomycin-induced pulmonary fibrosis. Antioxidants can reduce or prevent many of these side effects, and for some supplements the protective effect results from activities other than their antioxidant properties. Certain side effects, however, such as alopecia and myelosuppression, are not prevented... 

In laboratory animals, parenteral administration of organic and inorganic selenium (210 to 12,000 ig/kg) has been shown to protect against cisplatin-induced nephrotoxicity. Protection occurs without apparent inhibition of the antineoplastic activity of cisplatin, although this may be attributed to the fact that selenium administration allows for higher doses of cisplatin to be used. Additionally, selenium administration reduces cisplatin-induced myelosuppression. This raises a concern similar to that with administering cisplatin with thiol compounds, i.e., that the reduction of myelosuppression may indicate that selenium can also interfere with the antitumor activity of cisplatin. Selenium, with chemical properties similar to those of sulfur, can bind with platinum and... 

The mutagenic properties of cisplatin (resulting in both frame-shift and base-substitution mutations) are also pointing towards a (major) interaction with DNA48). 

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