Comparison of Triazines as Inhibitors of L1210 Dihydrofolate Reductase and of L1210 Cells Sensitive and Resistant to Methotrexate

摘要: The inhibition of dihydrofolate reductase from L1210 leukemia cells as well the intact cells, both sensitive and resistant, to methotrexate by over 100, 4,6-diamino-2,2-dihydro-2,2-dimethyl-1-(X-phenyl)- s -triazines was studied. Quantitative structure-activity relationships were derived for three systems. These equations, based on a set congeners having range in lipophilicity about 700,000,000 octanol-water scale, delineate inhibitory potency triazines relation their hydrophobicity. data demonstrate that there is close parallel between way isolated respond triazines. However, resistant behave an entirely different manner, which suggests passive diffusion into dominates relationship. optimum (π) triazine substituents purified 1.76 2.11; it 1.45 1.83, ∼6.