title: Combined distance geometry analysis of dihydrofolate reductase inhibition by quinazolines and triazines.
abstract: Guided by the success of distance geometry in explaining the inhibition of dihydrofolate reductase by 68 quinazolines, we have made a combined analysis on the inhibition of rat liver dihydrofolate reductase by 33 triazines and 15 quinazolines. The model gave a fit having the correlation coefficient 0.892 and root mean square (rms) deviation 0.596 in log (1/C50) units. The model was applied to predict the biological activity of 91 compounds. The predicted values showed an rms deviation of 0.907 and a correlation coefficient of 0.790. The present study suggested the synthesis of some triazines as possible potent dihydrofolate inhibitors. The site geometry was compared with the crystal structure of a triazine bound to chicken liver dihydrofolate reductase, and a good correlation has been found.
mesh_terms: D055598:Chemical Phenomena; D002621:Chemistry; D005493:Folic Acid Antagonists; D008968:Molecular Conformation; D011799:Quinazolines / Q000494:pharmacology*; D013291:Streptococcus / Q000201:enzymology; D013329:Structure-Activity Relationship; D014227:Triazines / Q000494:pharmacology*
chemical_list: D005493:Folic Acid Antagonists; D011799:Quinazolines; D014227:Triazines