Cholic acid–carboplatin compounds (CarboChAPt) as models for specific drug delivery: synthesis of novel carboplatin analogous derivatives and comparison of the cytotoxic properties with corresponding cisplatin compounds

Paschke, Ralf; Kalbitz, Jutta; Paetz, Christian; Luckner, Martin; Mueller, Thomas; Schmoll, Hans Joachim; Mueller, Helmut; Sorkau, Eduard; Sinn, Ekkehard

doi:10.1016/s0162-0134(03)00024-2

Cited by 48 publications

(31 citation statements)

References 21 publications

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“…Complex 4 was excluded because of its similar cytotoxic efficacy with complex 3. In comparison to literature data [20][21][22] and as can be seen from Table 3, the amount of platinum uptake for complexes 1-3 was very low. This could be a consequence of the acidic carboxylic proton dissociating in the culture media and yielding a charged species that does not easily penetrate the hydrophobic cellular membrane.…”

Section: Inversion Of Configuration At the Sulfur Atomsupporting

confidence: 48%

“…After the product was filtered off, it was washed with cold water (3 · 1 ml) and dried on air. Yield: 191 mg, 81% (ratio of diastereoisomers 66:34% 21.60 (C 10 ), 23.2 (C 11 ), 25.2 (C 8 ), 29.6 (C 3 ), 32.2 (C 2 ), 41.1 (C 9 ), 51.7 (C 6 ), 55.2 (C 4 ), 171.2 (C 5 ), 174.6 (C 7 ); isomer 3B: d 21.57 (C 1 ), 21.60 (C 10 ), 23.2 (C 11 ), 25.2 (C 8 ), 29.8 (C 3 ), 31.8 (C 2 ), 41.1 (C 9 ), 51.7 (C 6 ), 54.1 (C 4 ), 171.5 (C 5 ), 174.6 (C 7 ). 195 …”

Section: Synthesismentioning

confidence: 99%

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Platinum(II) complexes with l-methionylglycine and l-methionyl-l-leucine ligands: Synthesis, characterization and in vitro antitumoral activity

Kaluđerović

Schmidt

Paschke

et al. 2007

Journal of Inorganic Biochemistry

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Section: Inversion Of Configuration At the Sulfur Atomsupporting

confidence: 48%

Section: Synthesismentioning

confidence: 99%

Platinum(II) complexes with l-methionylglycine and l-methionyl-l-leucine ligands: Synthesis, characterization and in vitro antitumoral activity

Kaluđerović

Schmidt

Paschke

et al. 2007

Journal of Inorganic Biochemistry

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“…Interest in these compounds could be extended to the regional treatment of tumors located outside of the enterohepatic circuit. In this respect, a platinated cholic acid derivative, obtained by coupling this bile acid to a carboplatin analog, has been shown to induce apoptosis in a human testicular cancer cell line (Paschke et al, 2003). In these cases, the pharmacological interest of Bamets is assumed to be due to the ability of the liver to efficiently take up and secrete into bile the fraction of the administered drug that may escape from the tumor and reach the general circulation during regional chemotherapy Larena et al, 2001).…”

mentioning

confidence: 99%

Proapoptotic Effect on Normal and Tumor Intestinal Cells of Cytostatic Drugs with Enterohepatic Organotropism

Monte¹,

Ballestero²,

Briz³

et al. 2005

J Pharmacol Exp Ther

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The proapoptotic effect of cisplatin bile acid derivatives Bamet-R2 [cis-diamminechloro-cholylglycinate-platinum(II)] and Bamet-UD2 [cis-diammine-bisursodeoxycholate-platinum(II)], developed to treat liver and intestinal tumors, was investigated in vitro using human enterohepatic cells HepG2 (hepatoblastoma), LS 174T (colon adenocarcinoma), and its cisplatin-resistant subline LS 174T/R. Uptake by wild-type tumor cells was higher for Bamets than for cisplatin. In LS 174T/R cells, copper transporter-1 was down-regulated and multidrug resistance-associated protein-2 was up-regulated. Consequently, uptake and efflux of cisplatin, but not those of Bamets, were reduced and increased, respectively. The degree of necrosis (lactate dehydrogenase release) induced by these three drugs was small and similar in all cell types. In contrast, proapoptotic effect (caspase-3 activity and DNA fragmentation) was Bamet-UD2 Ͼ cisplatin Ͼ Bamet-R2 in HepG2 and LS 174T cells, but Bamet-UD2 Ͼ Bamet-R2 Ͼ Ͼ cisplatin in LS 174T/R cells. This effect was consistent with the ability of these compounds to form DNA-adducts (DNA-platination, changes in the DNA melting temperature, and MspI-induced restriction sequence cleavage). Oral administration of Bamet-UD2 to mice induced mild apoptosis in the small intestine (ileum Ͼ duodenum), which was not severe enough to modify its structure or function as determined by water absorption and glycocholic acid uptake by in situ perfused ileum. These results indicate that Bamet-UD2 overcomes the resistance to cisplatin when this is due in part to enhanced ability of intestinal tumors to reduce intracellular cisplatin contents. Moreover, its strong proapoptotic versus its weak pronecrotic effect together with its mild effect on normal tissues, including intestinal mucosa, may account for the high antitumor activity of Bamet-UD2 together with its very low toxicity.

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“…A homing moiety such as galactose [41,42] and bile acid [43,44] for liver and estrogen derivatives for estrogen receptor (ER) positive tissues [45] such as breast have been utilized to achieve tissue specificity. For example, platinumpolymer conjugates with attached galactose exhibited cellspecific cytotoxic activity against human hepatoma cells.…”

Section: Cisplatin Analogs With Carrier Groupsmentioning

confidence: 99%

Platinum Complexes as Anticancer Agents

Kostova

2006

PRA

444

206

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The application of inorganic chemistry to medicine is a rapidly developing field, and novel therapeutic and diagnostic metal complexes are now having an impact on medical practice. Advances in biocoordination chemistry are crucial for improving the design of compounds to reduce toxic side effects and understand their mechanisms of action. Cisplatin, as one of the leading metal-based drugs, is widely used in the treatment of cancer. Significant side effects and drug resistance, however, have limited its clinical applications. Biological carriers conjugated to cisplatin analogs have improved specificity for tumor tissue, thereby reducing side effects and drug resistance. Platinum complexes with distinctively different DNA binding modes from that of cisplatin also exhibit promising pharmacological properties. This review focuses on recent advances in developing platinum anticancer agents with an emphasis on platinum coordination complexes.

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Cholic acid–carboplatin compounds (CarboChAPt) as models for specific drug delivery: synthesis of novel carboplatin analogous derivatives and comparison of the cytotoxic properties with corresponding cisplatin compounds

Cited by 48 publications

References 21 publications

Platinum(II) complexes with l-methionylglycine and l-methionyl-l-leucine ligands: Synthesis, characterization and in vitro antitumoral activity

Platinum(II) complexes with l-methionylglycine and l-methionyl-l-leucine ligands: Synthesis, characterization and in vitro antitumoral activity

Proapoptotic Effect on Normal and Tumor Intestinal Cells of Cytostatic Drugs with Enterohepatic Organotropism

Platinum Complexes as Anticancer Agents

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