 Chemical structure of Dicycloplatin | |
| Clinical data | |
|---|---|
| Trade names | Dicycloplatin |
| Other names | Platinum(2+) 1-carboxycyclobutanecarboxylate ammoniate (1:2:2), 1,1-Cyclobutanedicarboxylic acid, compd. with (sp-4-2)-diammine(1,1-cyclobutanedi(carboxylato-kappaO)(2-))platinum (1:1) |
| Routes of administration | Intravenous |
| Pharmacokinetic data | |
| Bioavailability | 100% (IV) |
| Protein binding | < 88.7% |
| Eliminationhalf-life | 24.49 - 108.93 hours |
| Excretion | Renal |
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| Chemical and physical data | |
| Formula | C12H20N2O8Pt |
| Molar mass | 515.382 g·mol−1 |
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Dicycloplatin is achemotherapy medication used to treat a number of cancers which includes thenon-small-cell lung carcinoma andprostate cancer.[1]
Some side effects which are observed from the treatment by dicycloplatin arenausea,vomiting,thrombocytopenia,neutropenia,anemia,fatigue,loss of appetite,liver enzyme elevation andalopecia. The drug is aplatinum-based antineoplastic, and it works by causing mitochondrial dysfunction which leads tocell death.[2]
Dicycloplatin was developed in China and it was used forphase I human trial clinical in 2006. The drug was approved for chemotherapy by the Chinese FDA in 2012.[3]
Dicycloplatin can inhibit the proliferation of tumor cells via the induction ofapoptosis. It is used to treat a number types of cancer which arenon-small-cell lung carcinoma andprostate cancer.[2]
Similar tocisplatin andcarboplatin, dicycloplatin also contains some side effects, which arenausea,vomiting,thrombocytopenia,neutropenia,anemia,fatigue,loss of appetite,liver enzyme elevation, andalopecia. However, with doses up to 350 mg/m(2), there is no significant toxicity; these effects are observed only at higher doses. Furthermore, the nephrotoxicity of dicycloplatin is reported to be less than that ofcisplatin, and its myelosuppressive potency is similar to that ofcarboplatin.[4]
Dicycloplatin consists ofcarboplatin and cyclobutane-1,1-dicarboxylic acid (CBDC) linked by thehydrogen bond. In the structure of dicycloplatin, there are two types of bond: O-H...O is the bond between thehydroxyl group of CBDC with carboxyl oxygen atom. It creates the one-dimensional polymer chain of carboplatin and CBDC. The second one is N-H...O which links between theammonia group ofcarboplatin and oxygen of CBDC. It forms the two-dimensional polymer chain of carboplatin and CBDC. In aqueous solution, the 2D-hydrogen bonded polymeric structure of dicycloplatin is destroyed. Firstly, the bond betweenammonia group ofcarboplatin and oxygen of CBDC breaks, thus inducing the formation of one-dimensional dicycloplatin. After that, the strong hydrogen bond breaks and creates an intermediate state of dicycloplatin. Finally, the rearrangement of different orientation of carboplatin and CBDC leads to the formation of intramolecularhydrogen bond and a supramolecule of dicycloplatin with two O-H...O and N-H...O is created.[5]
Similar tocarboplatin, dicycloplatin inhibits the proliferation of cancer cells by inducing cellapoptosis. When treated with dicycloplatin, some changes in the properties ofHep G2 cells are observed: the declination ofMitochondria Membrane Potential, the release ofcytochrome c from mitochondria to cytosol, the activation ofcaspase-9,caspase-3 and the decrease ofBcl-2.[2] Those phenomena indicate the role of mitochondrial in theapoptosis by intrinsic way.[6] Furthermore, the increase incaspase-8 activation is also observed. This can stimulate theapoptosis by activating downstreamcaspase-3[7] or by cleavingBid.[8] As a result, the cleavage of Bid (tBid) transfers to the mitochondria and induce mitochondrial dysfunction which promotes the release of cytochrome c from mitochondria to cytosol.[9] From the dicycloplatin-treatedHep G2 cell, an excessive amount ofreactive oxygen species was detected,[2] which plays an important role in the release ofcytochrome c. In the mitochondria, the release ofhemoprotein happens through 2-step process: Firstly, the dissociation ofcytochrome c from its binding tocardiolipin happens. Due to thereactive oxygen species, the cardiolipin is oxidized, thus reducing the cytochrome c binding and increase the concentration of free cytochrome c.[10]
