Inhibition by 5-(substituted-benzyl)-2,4-diaminopyrimidines of murine tumor (L5178Y) cell cultures sensitive to and resistant to methotrexate. Further evidence for the sensitivity of resistant cells to hydrophobic drugs.
Forty-three 5-(substituted-benzyl)-2,4-diaminopyrimidines have been studied as inhibitors of murine tumor cell cultures (L5178Y). Two types of cells were used--one resistant to methotrexate and one sensitive to methotrexate. The formulation of quantitative structure--activity relationships showed that the methotrexate-resistant cells are more sensitive to the more hydrophobic congeners. pi 0 for the sensitive cells is about 1.4, while pi 0 for the methotrexate-resistant cells is above 3. These results are similar to those found for 2,4-diaminotriazines (Selassie, C.D.; Guo, Z. R.; Hansch, C.; Khwaja, T. A.; Pentecost, S. J. Med. Chem. 1982, 25, 157).
D000818:Animals; D000970:Antineoplastic Agents; D002478:Cells, Cultured; D055598:Chemical Phenomena; D002621:Chemistry; D002626:Chemistry, Pharmaceutical; D004351:Drug Resistance; D007940:Leukemia L5178 / Q000188:drug therapy*; D007942:Leukemia, Experimental / Q000188:drug therapy*; D008727:Methotrexate / Q000494:pharmacology*; D051379:Mice; D011743:Pyrimidines / Q000494:pharmacology*; D012995:Solubility
D000970:Antineoplastic Agents; D011743:Pyrimidines; D008727:Methotrexate