Simplified Tetrandrine Congeners as Possible Antihypertensive Agents with a Dual Mechanism of Action
| Autor: | M. Dolores Ivorra, Raquel Miquel, Bruce K. Cassels, M. Pilar D'ocon, Patricio Iturriaga-Vásquez |
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| Rok vydání: | 2003 |
| Předmět: |
Pharmacology
Stereochemistry Calcium channel Alkaloid Organic Chemistry Antagonist Pharmaceutical Science Analytical Chemistry Tetrandrine chemistry.chemical_compound Complementary and alternative medicine Mechanism of action chemistry Drug Discovery medicine Radioligand Prazosin Molecular Medicine heterocyclic compounds medicine.symptom Coclaurine medicine.drug |
| Zdroj: | Journal of Natural Products. 66:954-957 |
| ISSN: | 1520-6025 0163-3864 |
| Popis: | 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 alpha(1)-adrenergic radioligand [(3)H]prazosin or the calcium channel radioligand [(3)H]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. |
| Databáze: | OpenAIRE |
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