Inhibition of 2,3-oxidosqualene: beta-amyrin-cyclase, S-adenosyl-L-methionine: cycloartenol C-24-methyltransferase and cycloeucalenol: obtusifoliol isomerase by rationally designed molecules containing a tertiary amine function.
25-Azacycloartanol (I), 2-aza-2-dihydrosqualene (II) and Tridemorph (2,6-dimethyl-N-tridecylmorpholine) (III) are potent inhibitors of higher plant sterol biosynthesis. The first two molecules have been designed using rational enzymological concepts. I, II and III were shown to inhibit the S-adenosyl-L-methionine: cycloartenol C-24-methyltransferase, the 2,3-oxidosqualene: beta-amyrin-cyclase and the cycloeucalenol: obtusifoliol isomerase, respectively. Inhibition was demonstrated either in vivo on bramble cell suspensions or in vitro on microsomes from maize seedlings. Each inhibitor has been shown to have a high affinity for its presumed enzymic target and only negligible inhibitory action on the other two enzymes. The applications of these results to further physiological studies are discussed.
D055598:Chemical Phenomena; D002621:Chemistry; D007887:Fabaceae; D005659:Fungicides, Industrial / Q000494:pharmacology; D019751:Intramolecular Transferases; D007535:Isomerases / Q000037:antagonists & inhibitors*; D008780:Methyltransferases / Q000037:antagonists & inhibitors*; D009025:Morpholines / Q000494:pharmacology; D010840:Phytosterols / Q000494:pharmacology; D010944:Plants / Q000201:enzymology*; D010946:Plants, Medicinal; D013185:Squalene / Q000031:analogs & derivatives / Q000494:pharmacology; D013251:Steroid Isomerases / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D003313:Zea mays
D005659:Fungicides, Industrial; D009025:Morpholines; D010840:Phytosterols; C015554:tridemorph; C040110:25-azacycloartanol; D013185:Squalene; C039926:2-aza-2-dihydrosqualene; D008780:Methyltransferases; C019609:S-adenosyl-L-methionine-cycloartenol methyltransferase; D007535:Isomerases; D013251:Steroid Isomerases; C039925:cycloeucalenol-obtusifol isomerase; D019751:Intramolecular Transferases; C039924:2,3-oxidosqualene-beta-amyrin-cyclase