Carboplatin structure

The platinum(IV) compound that has shown most promise is carboplatin (paraplatin), which received FDA approval in 1990. Features to note in its structure are the use of hydroxy and carboxylate groups to improve water solubility. As noted above, the ammine ligand has been found to need at least one hydrogen, possibly for hydrogen-bonding to phosphate groups in the DNA (Figure 3.116). 

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). ... 

Figure 1. Schematic structures of c/s- and frans-DDP, carboplatin and the model compound [PtCI(dien)]CI.

In general, Ru11 and Os11 arene complexes show promising cytotoxic activity against human ovarian cancer cell lines, some of them as potent as cisplatin and carboplatin. Some structure-activity relationships have been established... 

One of the great successes of transition metal compounds is Cisplatin. This compound, with a very simple structure (and, incidentally, not even a single carbon atom ), is one of the most successful anticancer dmgs [3]. After its serendipious discovery by B. Rosenberg, Cisplatin quickly gained clinical approval in 1978. It has inspired research efforts into literally thousands of Pt-containing compounds, from which two more have reached world-wide approval (Carboplatin and... 

T) Do direct chemical interactions occur between rescue agents and platinum compounds (such as the drugs cisplatin and carboplatin transpla-tin), and between the relevant model compounds (such as Ptn(dien), or perhaps the kinetically faster reacting Pd11 compounds) Which interaction products are formed in vivo (structure, kinetics) This topic has been largely neglected in the literature. 

Figure 17.5 Skeleton structures of (a) polypyrrolic photosensitizers (i) porphyrin, (ii) chlorine, (Hi) bacteriochlorin, (iv) phthalocyanine, (v) naphthalocyanine, (vi) texaphyrin (b) examples of metalloderivatives (c) photosensitizers incorporating the metallodrug moieties (x-xii) cisplatin- and/or carboplatin-like structures, (xiii) iron sulphur nilrosy cluster...

Figure 22.11. Structures of platinum compounds. Cisplatin and carboplatin are active agents used in cancer chemotherapy. Transplatin is inactive against tumors.

These reactions can be used to understand many of the structure-function relationships among the approved drugs and those that have undergone clinical testing. For example, carboplatin retains the cis -diammineplatinum(II) center, but the chlorides have been replaced by the cyclobutanedicarboxylate ligand. The similar array of... 

Carboplatin is a cytotoxic platinium complex structurally related to cisplatin, which antitumor activity in vitro is qualitatively similar to that of cisplatin. Comparative trials with carboplatin alone or in combination with other chemotherapeutic agents suggest comparable efficacy with cisplatin in ovarian cancer. As with cisplatin, nausea and vomiting occur in many patients but symptoms are usually delayed for several hours and mild to moderate in severity. The dose limiting toxicity of carboplatin is myelosuppression enhanced by renal impairment, previous chemotherapy or in older patients. 

In order to avoid serious side effects of cisplatin (kidney- and neuro-toxicity) alternative Pt compounds have been developed. The most important of these is carboplatin in which the ci.s-chlorides are replaced by the 0-chelate, cyclobutanedicarboxylate but all of them have ligands with NH groups which facilitate the hydrogen bonding thought to stabilize the distortions of the DNA structure. 

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