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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
8
|
| pubmed:dateCreated |
1986-9-17
|
| pubmed:abstractText |
The synthesis, physical properties, and antitumor activity of the cis-, d,l-trans-, d-trans-, and l-trans- stereoisomers of 1,2-diaminocyclohexane tetrachloroplatinum(IV) are described. The objective of the study was to produce a platinum complex with activity against cisplatin-resistant tumor cells and with suitable pharmaceutical properties for formulation development. The isomers had the following solubilities in saline: cis-, 2 mg/ml; d,l-trans-, 6.5 mg/ml; and d-trans- and l-trans-, 15-16 mg/ml. The four complexes showed slightly better activity than cisplatin against the ip implanted murine L1210 leukemia. In contrast to cisplatin, all complexes produced significant increases in life span against L1210/cisplatin, a subline of L1210 with acquired resistance to cisplatin. However, the cis- isomer was less active against L1210/cisplatin. The d,l-trans- isomer (tetraplatin) was selected for further studies based on greater ease for large-scale synthesis. It showed superior activity to cisplatin against P388/cisplatin and like cisplatin showed significant and reproducible activity against the ip implanted B16 melanoma, ip implanted M5076 sarcoma, ip implanted P388 leukemia, and MX-1 human breast xenograft implanted under the renal capsule. Purity and stability (greater than 24 hours in saline) were evaluated by high-performance liquid chromatography and found to be suitable for development of a parenteral dosage form. Preliminary studies in a rat model (to be reported elsewhere) showed it to be less nephrotoxic than cisplatin on a molar basis and worthy of further study.
|
| pubmed:grant | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Aug
|
| pubmed:issn |
0361-5960
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
70
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
997-1002
|
| pubmed:dateRevised |
2007-11-14
|
| pubmed:meshHeading |
pubmed-meshheading:3731155-Animals,
pubmed-meshheading:3731155-Antineoplastic Agents,
pubmed-meshheading:3731155-Body Weight,
pubmed-meshheading:3731155-Breast Neoplasms,
pubmed-meshheading:3731155-Cell Line,
pubmed-meshheading:3731155-Cisplatin,
pubmed-meshheading:3731155-Drug Evaluation, Preclinical,
pubmed-meshheading:3731155-Drug Resistance,
pubmed-meshheading:3731155-Humans,
pubmed-meshheading:3731155-Leukemia L1210,
pubmed-meshheading:3731155-Leukemia P388,
pubmed-meshheading:3731155-Melanoma,
pubmed-meshheading:3731155-Mice,
pubmed-meshheading:3731155-Mutation,
pubmed-meshheading:3731155-Organoplatinum Compounds,
pubmed-meshheading:3731155-Rats,
pubmed-meshheading:3731155-Sarcoma, Experimental,
pubmed-meshheading:3731155-Stereoisomerism
|
| pubmed:year |
1986
|
| pubmed:articleTitle |
Synthesis, physical properties, and antitumor activity of tetraplatin and related tetrachloroplatinum(IV) stereoisomers of 1,2-diaminocyclohexane.
|
| pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, U.S. Gov't, P.H.S.
|