Abstract
The structure activity relationships were studied on newly synthesized 1,4-dihydropyridine derivatives possessing a 1-pentyl group at the 4-position, and 3-pyridylpropylester was found to be one of the effective fragments for overcoming P-glycoprotein mediated multidrug-resistance (MDR) in cultured human cancer cells, in vitro. 3-Pyridylpropylester was also found to be one of the effective fragments for increasing the life span of P-glycoprotein overexpressing MDR P388 leukemia-bearing mice, in vivo. All compounds had weak calcium antagonistic activities, but there appeared no relationship between MDR reversing effect and calcium antagonistic activity.
MeSH terms
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ATP Binding Cassette Transporter, Subfamily B, Member 1 / antagonists & inhibitors
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ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
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Animals
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Antineoplastic Combined Chemotherapy Protocols / chemical synthesis
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Antineoplastic Combined Chemotherapy Protocols / chemistry
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Antineoplastic Combined Chemotherapy Protocols / pharmacology
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Calcium / antagonists & inhibitors
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Combinatorial Chemistry Techniques
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Dihydropyridines / chemical synthesis
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Dihydropyridines / chemistry
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Dihydropyridines / pharmacology*
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Drug Resistance, Multiple*
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Humans
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Inhibitory Concentration 50
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Leukemia P388 / drug therapy
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Mice
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Structure-Activity Relationship
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Survival Rate
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Transfection
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Tumor Cells, Cultured / drug effects
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Vincristine / pharmacology
Substances
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ATP Binding Cassette Transporter, Subfamily B, Member 1
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Dihydropyridines
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Vincristine
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Calcium