Abstract
P-glycoprotein (P-gp) is an important factor in the development of multidrug resistance (MDR) in cancer cells. In literature reports, a thieno[2,3-d]pyrimidine (QB13) was described as P-gp modulator and opposed effects on the cell accumulation of distinct P-gp substrates were postulated. On the basis of this lead structure, a series of 2-alkylthio-4-aminothieno[2,3-d]pyrimidines was prepared and tested in a daunorubicin accumulation assay. Modulation of substrate specificity was shown for selected compounds in cytotoxicity (MTT) assays.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism*
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Antibiotics, Antineoplastic / metabolism
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Cell Line, Tumor
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Crystallography, X-Ray
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Daunorubicin / metabolism
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Drug Resistance, Neoplasm
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Humans
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Molecular Conformation
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Pyrimidines / chemical synthesis
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Pyrimidines / chemistry*
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Pyrimidines / pharmacology
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Quinazolines / chemical synthesis
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Quinazolines / chemistry
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Quinazolines / pharmacology
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Substrate Specificity
Substances
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ATP Binding Cassette Transporter, Subfamily B, Member 1
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Antibiotics, Antineoplastic
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Pyrimidines
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Quinazolines
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thienopyrimidine
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Daunorubicin