Active efflux of antifungal, antibacterial and anticancer drugs by broad-specificity multidrug resistance (MDR) transporters are major obstacles to successful chemotherapy of infectious diseases and cancer. We evaluated the growth inhibitory and MDR modulatory effect of a series of 36 phenothiazines and related compounds, against Saccharomyces cerevisiae strains exhibiting different levels of expression of MDR transporters Pdr5p, Snq2p and Yor1p. Several newly synthesized derivatives were identified as substrates of Pdr5p as their growth inhibitory properties were potentiated by deletion of PDR5. They were synergistic with the antifungal ketoconazole at micromolar concentrations. The most active phenothiazines contained the amino group at the end of the alkylene chain substituent.
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Evidence ID | Analyze ID | Gene/Complex | Systematic Name/Complex Accession | Qualifier | Gene Ontology Term ID | Gene Ontology Term | Aspect | Annotation Extension | Evidence | Method | Source | Assigned On | Reference |
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Evidence ID | Analyze ID | Gene | Gene Systematic Name | Phenotype | Experiment Type | Experiment Type Category | Mutant Information | Strain Background | Chemical | Details | Reference |
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Evidence ID | Analyze ID | Gene | Gene Systematic Name | Disease Ontology Term | Disease Ontology Term ID | Qualifier | Evidence | Method | Source | Assigned On | Reference |
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Evidence ID | Analyze ID | Regulator | Regulator Systematic Name | Target | Target Systematic Name | Direction | Regulation of | Happens During | Regulator Type | Direction | Regulation Of | Happens During | Method | Evidence | Strain Background | Reference |
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Site | Modification | Modifier | Source | Reference |
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Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Allele | Assay | Annotation | Action | Phenotype | SGA score | P-value | Source | Reference | Note |
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Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Assay | Annotation | Action | Modification | Source | Reference | Note |
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Complement ID | Locus ID | Gene | Species | Gene ID | Strain background | Direction | Details | Source | Reference |
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Evidence ID | Analyze ID | Dataset | Description | Keywords | Number of Conditions | Reference |
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