Synthesis, fungicidal activity, and sterol 14α-demethylase binding interaction of 2-azolyl-3,4-dihydroquinazolines on Penicillium digitatum.
A series of new 2-azolyl-3,4-dihydroquinazolines 6 was synthesized by direct cyclization of imidazole or 1,2,4-triazole with carbodiimides 4, which were obtained from aza-Wittig reaction of iminophosphorane 3 with isocyanate. The preliminary bioassay results demonstrated that most of the 2-imidazolyl-3,4-dihydroquinazolines 6a-6i exhibited good to significant fungicidal activity against  Penicillium digitatum , whereas 2-triazolyl-3,4-dihydroquinazolines 6j-6t exhibited low fungicidal activity. Some of the 2-imidazolyl-3,4-dihydroquinazolines 6a-6i also exhibited strong binding interaction with the cytochrome P450-dependent sterol 14α-demethylase (CYP51). For example, compound 6e showed the best fungicidal activity against P. digitatum with IC(50) = 4.14 μg/mL and the best CYP51 binding activity with K(d) = 0.34 μg/mL, both superior to those of the agricultural fungicide triadimefon.
Key Laboratory of Pesticide and Chemical Biology of the Ministry of Education, College of Life Science, Central China Normal University, Wuhan 430079, China.
Wen-Jin
WJ
Li
Qian
Q
Li
De-Li
DL
Liu
Ming-Wu
MW
Ding
D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D005659:Fungicides, Industrial / Q000138:chemical synthesis / Q000494:pharmacology*; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010407:Penicillium / Q000187:drug effects* / Q000201:enzymology; D011485:Protein Binding; D011799:Quinazolines / Q000138:chemical synthesis / Q000494:pharmacology*; D058886:Sterol 14-Demethylase / Q000378:metabolism*; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
D005659:Fungicides, Industrial; D007093:Imidazoles; D011799:Quinazolines; D014230:Triazoles; C032910:triadimefon; C045575:1,2,4-triazole; C029899:imidazole; D003577:Cytochrome P-450 Enzyme System; D058886:Sterol 14-Demethylase