Quantitative structure-activity relationship of antifolate inhibition of bacteria cell cultures resistant and sensitive to methotrexate
| Autor: | Clara S. Genther, Corwin Hansch, Cynthia D. Strong, Eugene A. Coats, Cynthia Dias Selassie |
|---|---|
| Rok vydání: | 1985 |
| Předmět: |
Lactobacillus casei
Chemical Phenomena Biological Transport Active medicine.disease_cause Bacterial cell structure Structure-Activity Relationship chemistry.chemical_compound Drug Discovery Dihydrofolate reductase Escherichia coli medicine Structure–activity relationship biology Triazines Chemistry Drug Resistance Microbial biology.organism_classification Lacticaseibacillus casei Methotrexate Pyrimethamine Pyrimidines Biochemistry Enzyme inhibitor Antifolate biology.protein Folic Acid Antagonists Molecular Medicine Mathematics medicine.drug |
| Zdroj: | Journal of Medicinal Chemistry. 28:1910-1916 |
| ISSN: | 1520-4804 0022-2623 |
| Popis: | Sets of 5-(substituted benzyl)-2,4-diaminopyrimidines and 4,6-diamino-1,2-dihydro-2,2-dimethyl-1-(3-substituted phenyl)-s-triazines as well as several other antifolates were tested as inhibitors of Escherichia coli dihydrofolate reductase and E. coli cell cultures both sensitive and resistant to methotrexate. From the results quantitative structure-activity relationships (QSAR) were formulated. The triazines were found to inhibit sensitive and resistant cell cultures to the same degree, but the benzylpyrimidines showed marked differences against the two types of cells. Increased hydrophobicity produced benzylpyrimidines more active against the resistant E. coli cell. Metroprine did not discriminate between the two types of cells cultures, but pyrimethamine and 2,4-diamino-6-(2,5-dimethoxybenzyl)-5-methylpyrido[2,3-d]pyrimidin e (BW 301U) did. The results are compared with triazines and benzylpyrimidines acting on Lactobacillus casei and murine tumor cells sensitive and resistant to methotrexate. QSAR is shown to be an effective means for detecting receptor differences. |
| Databáze: | OpenAIRE |
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