Calmodulin inhibitors from Leucophyllum ambiguum.

Activity-directed fractionation of a CH(2)Cl(2)-MeOH (1:1) extract of Leucophyllum ambiguum led to the isolation of two new lignans designated with the trivial names of 2'-methoxykobusin (1) and 2'-methoxy-4' '-hydroxydemethoxykobusin (2). In addition, the known compounds kobusin (3), 2',2' '-dimethoxysesamin (4), trans-cinnamic acid, apigenin, and apigetrin were obtained. The identification of the novel analogues 1 and 2 was accomplished by spectral methods. The structure of 1 was unequivocally confirmed by X-ray analysis. Compounds 1-4 interacted with bovine-brain calmodulin and inhibited the activation of the calmodulin-dependent enzyme cAMP phosphodiesterase.