Abstract
To improve cytotoxicity of 10-deoxy-10-C-morpholinoethyl docetaxel analogues against various tumor cell lines including resistant cells expressing P-glycoprotein (P-gp), we modified the 7-hydroxyl group to hydrophobic groups (methoxy, deoxy, 6,7-olefin, alpha-F, 7-beta-8-beta-methano, fluoromethoxy). Among these analogues, the 7-methoxy analogue showed the strongest cytotoxicity. This analogue showed potent activity against B16 melanoma BL6 in vivo by oral administration.
MeSH terms
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Administration, Oral
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Animals
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Antineoplastic Agents, Phytogenic / administration & dosage
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Antineoplastic Agents, Phytogenic / chemical synthesis*
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Antineoplastic Agents, Phytogenic / pharmacology
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Cell Division / drug effects
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Combinatorial Chemistry Techniques
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Docetaxel
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Drug Screening Assays, Antitumor
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Humans
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Inhibitory Concentration 50
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Lung Neoplasms / drug therapy
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Lung Neoplasms / pathology
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Melanoma, Experimental / drug therapy
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Mice
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Mice, Inbred C57BL
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Morpholines / administration & dosage
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Morpholines / chemical synthesis
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Morpholines / pharmacology*
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Paclitaxel / administration & dosage
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Paclitaxel / analogs & derivatives*
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Paclitaxel / chemical synthesis
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Paclitaxel / pharmacology*
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Solubility
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Structure-Activity Relationship
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Survival Rate
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Taxoids*
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Tumor Cells, Cultured / drug effects
Substances
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10-deoxy-10-C-morpholinoethyl docetaxel
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Antineoplastic Agents, Phytogenic
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Morpholines
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Taxoids
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Docetaxel
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Paclitaxel