Abstract
Starting from lead compounds 12b and 28b, previously characterized as P-glycoprotein (P-gp) modulating agents, two series of new compounds were investigated. Compounds 14a, b and 15a, b displayed high P-gp modulating activity in the submicromolar range (EC 50 values from 0.25 to 0.80 microM). Moreover, amino derivatives 23- 27 showed EC 50 values ranging from 0.085 to 0.90 microM. In the pyridyl series, the best result has been obtained for 4-pyridyl derivative 17b (EC 50 = 0.85 microM). The best P-gp modulating agents 14a, b, 15a, b, and 23- 27 also have been studied for determining their breast cancer resistance protein (BCRP) inhibition activity. The results demonstrated that only the amino derivatives 23- 27 displayed moderate BCRP inhibition 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 / biosynthesis
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ATP Binding Cassette Transporter, Subfamily G, Member 2
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ATP-Binding Cassette Transporters / antagonists & inhibitors
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Benzene Derivatives / chemical synthesis*
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Benzene Derivatives / pharmacokinetics
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Benzene Derivatives / pharmacology
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Biological Transport
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Cell Line, Tumor
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Cell Membrane Permeability
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Drug Resistance, Neoplasm
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Drug Screening Assays, Antitumor
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Humans
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Methylamines / chemical synthesis*
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Methylamines / pharmacokinetics
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Methylamines / pharmacology
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Neoplasm Proteins / antagonists & inhibitors
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Pyridines / chemical synthesis
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Pyridines / pharmacokinetics
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Pyridines / pharmacology
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Structure-Activity Relationship
Substances
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ABCG2 protein, human
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ATP Binding Cassette Transporter, Subfamily B, Member 1
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ATP Binding Cassette Transporter, Subfamily G, Member 2
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ATP-Binding Cassette Transporters
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Benzene Derivatives
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Methylamines
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Neoplasm Proteins
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Pyridines