INHIBITION OF HIGHER-PLANT 2,3-OXIDOSQUALENE CYCLASES BY NITROGEN-CONTAINING OXIDOSQUALENE ANALOGS

10-Aza-10,11-dihydro-2,3-oxidosqualene (10 N-OS), 19-aza-18,19,22,23-t etrahydro-2,3-oxidosqualene (19 N-OS) and 23-aza-22,23-dihydro-2,3-oxi dosqualene (23 N-OS), designed as analogues of carbocationic intermedi ates involved in the reaction pathway of 2,3-oxidosqualene-cycloarteno l cyclase (OSCC) and/or 2,3-oxidosqualene-beta-amyrin cyclase (OS beta AC), and which could possibly be cyclase activated, were shown to be novel inhibitors of both OSCC and OS beta AC in maize and pea microsom es. 10 N-OS had low activity on both plant cyclases with an I-50 varyi ng from 60 to 200 mu M. 19 N-OS was active on both OSCC (I-50 = 40 mu M) and OS beta AC (I-50 = 15 mu M), but there was no evidence of enzym e activation. 23 N-OS was also an efficient inhibitor of OS beta AC (I -50 = 1 mu M) and OSCC (I-50 = 3 mu M), suggesting that it presumably acts as a mimic of the initial C-2 carbocation intermediate involved i n the cyclization catalysed by both cycloartenol- and beta-amyrin-cycl ases. Copyright (C) 1996 Elsevier Science Ltd