CBDCA

In acidic aqueous solution the displacement of 1,1-cyclobutanedicar-boxylate (cbdca2-) from [Pt(cbdca)(NH3)2] (Figure 1) resembles the successive displacements of two monodentate carboxylates [18]. Rate constants of 8 x 10 5 s-1 and 8.0 x 10 4 s-1 (298.2 K) were found for the ring-opening step of nonprotonated and protonated species, respectively. 

Pt Carboplatin [Pt(NH3)2(CBDCA)] CBDCA= cyclobutanedicarboxylic acid Anticancer agent... 

Fujii M, Nameki H, Kawaura M, et al. A dose finding study of carboplatin (CBDCA) + UFT in head and neck cancer. ProcAm Soc Clin Oncol 1998 18 406a (abstr 1564). 

Choy H, DeVore RF, Porter LL, et al. Phase I trial of outpatient weekly docetaxel (DTX) Carboplatin (CBDCA) and concurrent thoracic radiation therapy (TRT) for stage III unresectable non-small-cell lung cancer A Vanderbilt Cancer Center Affiliate Network (VCCAN) Trial. Pro Am Soc Clin Oncol 1999 18 475a (abstract 1833). 

Murakami H, Kubota K, Ohe Y, et al. Phase I study of weekly docetaxel (DTX) and carboplatin (CBDCA) with concurrent thoracic radiotherapy (TRT) for stage III non-small cell lung cancer (NSCLC). Lung Cancer 2000 29(Suppl 1) 111 (abstract 367). 

Jacobs MC, Eisenberger M, Oh MC, et al. Carboplatin (CBDCA) and radiotherapy for stage IV carcinoma of the head and neck a phase I-II study. Int J Radiat Oncol Biol Phys 1989 17 361-363. 

Fig. 2. Structure of some promising platinum antitumor drugs. CBDCA (upper left) is already routinely used in the clinic (22).

In fact, the very recent 195Pt NMR results of Bancroft et al. (41) indicate that, in agreement with Miller and House (36c), most likely [cis-Pt(NH3)2Cl(H20)]+ is the predominant species that reacts with biomolecules (at least with DNA). Other Pt amine compounds that are antitumor active have different kinetics of the hydrolysis reactions, and usually react much slower. The second-generation drug CBDCA (Fig. 2) is known to hydrolyze (in a 1 mAf solution) with a half-life at 37°C of a few days (41a) (compared to only 1 hour for cis-Pt). 

The kinetics of substitution of the chelate group by tu, glutathione, and guanosine-5 -monophosphate and, in the case of the first two compounds by L-Met, on the compounds [Pt(dach)(CBDCA)], [Pt(dach)(gly)j+, and [Pt(dach)(L-Met)]+ have been investigated. Direct substitution of the chelate was observed and the nature of the donor atoms of the chelate (O-O, N-O, or S-N) plays an important role. Large... 

Ring-opened adducts of carboplatin can form not only from reactions with nucleotides, but also by the attack of sulfur amino acids [44]. Reactions with thioether ligands are much more rapid compared with thiols. Surprisingly very stable ring-opened species such as [Pt(CBDCA-0)(NH3)2(L-HMet-S)] are formed, which has a half-life for Met-S,N closure of 28 h at 310 K. Such an intermediate could also play a role in the biological activity of this drug. 

Lind MJ, McGregor J, Timms MS, Brown D, Palmer P. Comparative toxicity of cisplatin, carboplatin (CBDCA) and iproplatin (CHIP) in combination with cyclophosphamide in patients with advanced epithelial ovarian cancer. Eur J Cancer Clin Oncol 1988 24(9) 1471-9. 

Sharma H, Thatcher N, Baer J, Zaki A, Smith A, McAucliffe CA, Crowther D, Owens S, Eox BW. Blood clearance of radioactively labeled cis-diammine 1,1-cyclobutane dicarboxylate platinum [II] [CBDCA] in cancer patients. Cancer Chemother Pharmacol. 1983 11[1] 5-7... 

Abbreviations 1,1-CBDCA, 1,1-cyclobutanedicarboxylate dach, 1,2-diaminocyclohexane TMA, 1,2,4-benzenetricarboxylate 1,1-damch, 1,1-diaminomethylcyclohexane en, 1,2-diaminoethane. 

Cdrboplatin, Carboplatin, Poraplatin, CBDCA, JM8, NSC-241240, ris-diammine( I. I -cyclobulanedicarboxala-... 

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