Inhibition of 2,3-oxidosqualene: β-amyrin-cyclase, S-adenosyl-l-methionine: cycloartenol C-24-methyltransferase and cycloeucalenol: obtusifoliol isomerase by rationally designed molecules containing a tertiary amine function

Abstract

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: β- 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.