Artículos de revistas
Simplified Tetrandrine Congeners as Possible Antihypertensive Agents with a Dual Mechanism of Action
Fecha
2003-02-07Registro en:
J. Nat. Prod., Vol. 66, p. 954-957, 2003.
0163-3864
Autor
Iturriaga-Vásquez, Patricio
Miquel, Raquel
Ivorra, M. Dolores
D’Ocon, M. Pilar
Cassels Niven, Bruce
Institución
Resumen
A series of O- and/or N-substituted derivatives of (()-coclaurine (1a) were synthesized as simplified
structural mimics of the antihypertensive alkaloid tetrandrine (2) and assayed for binding to brain cortical
sites labeled with the R1-adrenergic radioligand [3H]prazosin or the calcium channel radioligand [3H]-
diltiazem. The introduction of O-benzyl groups on the coclaurine molecule, which exhibits only adrenergic
antagonist activity, led to the appearance of calcium channel blocking activity comparable to that of
tetrandrine while retaining adrenolytic activity in the same concentration range. Contraction of aortal
rings with noradrenaline or KCl was relaxed more potently by some of these coclaurine derivatives than
by tetrandrine, suggesting leads for the development of novel antihypertensive drugs with a dual
mechanism of action.