Source:http://linkedlifedata.com/resource/pubmed/id/10377224
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
12
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pubmed:dateCreated |
1999-7-8
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pubmed:abstractText |
Analogues of the antitumor drug S 16020-2 modified at the 9, 10, or 11 position were synthesized and evaluated in vitro and in vivo on the P388 leukemia and B16 melanoma models. Starting from 9-methoxy-5, 11-dimethyl-6H-pyrido[4,3-b]carbazole-1-carboxylic acid ethyl ester, the 11-CH3 analogue of 9-hydroxy-5,6-dimethyl-6H-pyrido[4, 3-b]carbazole-1-carboxylic (2-(dimethylamino)ethyl)amide (1), compound 4, was synthesized using a four-step sequence, whereas its 10-CH3 analogue 5 was prepared using a two-step pathway, starting from compound 1. Finally starting from the 9-OH compounds 1, 4, and 5, a series of variously 9-O-substituted derivatives were synthesized. In these series, the most active compounds resulted from esterification of the 9-OH group with various aliphatic diacids, which led to 9-O-CO-( )-COOH derivatives of 1, 4, and 5. For these compounds, the number of long-term surviving mice obtained at the optimal dose were 60-100% in the ip/iv P388 leukemia and 10-35% in the ip/ip B16 melanoma, corresponding to an improved therapeutic index with respect to 1 and 4. This high antitumor activity, with curative examples in both models, was not due to a higher cytotoxicity since these compounds were equally or slightly less potent in vitro than 1 and 4. The most active compounds were thus selected for further in vivo evaluation.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0022-2623
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
17
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pubmed:volume |
42
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2191-203
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pubmed:dateRevised |
2003-11-14
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pubmed:meshHeading |
pubmed-meshheading:10377224-Animals,
pubmed-meshheading:10377224-Antineoplastic Agents,
pubmed-meshheading:10377224-Cell Division,
pubmed-meshheading:10377224-Drug Screening Assays, Antitumor,
pubmed-meshheading:10377224-Ellipticines,
pubmed-meshheading:10377224-Inhibitory Concentration 50,
pubmed-meshheading:10377224-Leukemia P388,
pubmed-meshheading:10377224-Melanoma, Experimental,
pubmed-meshheading:10377224-Methylation,
pubmed-meshheading:10377224-Mice,
pubmed-meshheading:10377224-Neoplasm Transplantation,
pubmed-meshheading:10377224-Structure-Activity Relationship,
pubmed-meshheading:10377224-Tumor Cells, Cultured
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pubmed:year |
1999
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pubmed:articleTitle |
Synthesis of 9-O-substituted derivatives of 9-hydroxy-5, 6-dimethyl-6H-pyrido[4,3-b]carbazole-1-carboxylic acid (2-(dimethylamino)ethyl)amide and their 10- and 11-methyl analogues with improved antitumor activity.
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pubmed:affiliation |
Division Chimie A and Division de Cancérologie Expérimentale, Institut de Recherches Servier, 11 rue des Moulineaux, 92150 Suresnes, France.
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pubmed:publicationType |
Journal Article
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