title: Crystallography, quantitative structure-activity relationships, and molecular graphics in a comparative analysis of the inhibition of dihydrofolate reductase from chicken liver and Lactobacillus casei by 4,6-diamino-1,2-dihydro-2,2-dimethyl-1-(substituted-phenyl)-s-triazine s.
abstract: The inhibition of dihydrofolate reductase from chicken liver and from Lactobacillus casei has been studied with 4,6-diamino-1,2-dihydro-2,2-dimethyl-1-(substituted-phenyl)-s-triazines. It was found that for the chicken enzyme, inhibitor potency for 101 triazines was correlated by the following equation: log 1/Kiapp = 0.85 sigma tau' - 1.04 log (beta X 10 sigma tau' + 1) + 0.57 sigma + 6.36. The parameter tau' indicates that for certain substituents, tau = 0. In the case of the L. casei DHFR results, meta and para derivatives could not be included in the same equation. For 38 meta-substituted compounds, it was found that log 1/Kiapp = 0.38 tau'3-0.91 log (beta X 10 tau'3 + 1) + 0.71I + 4.60 and for 32 para-substituted phenyltriazines log 1/Kiapp = 0.44 tau'4-0.65 log (beta tau'4 + 1') - 0.90 upsilon + 0.69I + 4.67. In the L. casei equation, I is an indicator variable for substituents of the type CH2ZC6H4-Y and ZCH2C6H4-Y, where Z = O, NH, S, or Se. The parameter upsilon is Charton's steric parameter, which is similar to Taft's Es. The mathematical models obtained from correlation analysis are compared with stereo color graphics models.
mesh_terms: D000818:Animals; D002645:Chickens / Q000378:metabolism*; D003201:Computers; D005493:Folic Acid Antagonists; D007780:Lacticaseibacillus casei / Q000201:enzymology*; D008099:Liver / Q000201:enzymology*; D008433:Mathematics; D008958:Models, Molecular; D008968:Molecular Conformation; D011485:Protein Binding; D013329:Structure-Activity Relationship; D013762:Tetrahydrofolate Dehydrogenase / Q000378:metabolism; D014227:Triazines / Q000378:metabolism / Q000494:pharmacology*; D014961:X-Ray Diffraction
chemical_list: D005493:Folic Acid Antagonists; D014227:Triazines; D013762:Tetrahydrofolate Dehydrogenase