Bleaching activities of substituted pyrimidines and structure-activity comparison to related heterocyclic derivatives

The bleaching mode of action of 2,4-diphenyl pyrimidine derivatives was established by determination of the decreased formation of colored carotenoids and the accumulation of phytoene. Direct inhibition of the target enzyme phytoene desaturase was demonstrated by in vitro assays, which excludes p-hydroxyphenylpyruvate dioxygenase as a mode of action target. Furthermore, transgenic tobacco plants which express a bacterial phytoene desaturase that lacks the inhibition site also exhibited resitance to the pyrimidines. Structure-activity investigations of direct interaction of the pyrimidine derivatives with the target enzyme were carried out and established the importance of a defined length of the 5-substituent. Comparison of different central heterocycles with similar substitutions revealed that the inhibitory activities of pyrimidines and pyrimidinones were higher than the activities of pyridines and triazines. It is proposed that the important features for interaction/inhibition of phytoene desaturase are the negative charge at N-3 and the space filing of the 5-substituents. (C) 2001 Academic Press.