Abstract
Dodoneine (Ddn) is one of the active compounds identified from Agelanthusdodoneifolius, which is a medicinal plant used in African pharmacopeia and traditional medicine for the treatment of hypertension. In the context of a scientific program aiming at discovering new hypotensive agents through the original combination of natural product discovery and superacid chemistry diversification, and after evidencing dodoneine's vasorelaxant effect on rat aorta, superacid modifications allowed us to generate original analogues which showed selective human carbonic anhydrase III (hCA III) and L-type Ca2+ current inhibition. These derivatives can now be considered as new lead compounds for vasorelaxant therapeutics targeting these two proteins.
Keywords:
L-type calcium channel; carbonic anhydrase; dodoneine; molecular diversity; superacid.
MeSH terms
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Animals
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Antihypertensive Agents / chemistry*
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Antihypertensive Agents / isolation & purification
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Antihypertensive Agents / pharmacology
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Aorta / drug effects*
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Aorta / metabolism
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Aorta / physiopathology
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Biological Products
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Blood Pressure / drug effects
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Calcium Channels, L-Type / metabolism
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Carbonic Anhydrase III / metabolism
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Carbonic Anhydrase Inhibitors / chemistry*
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Carbonic Anhydrase Inhibitors / isolation & purification
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Carbonic Anhydrase Inhibitors / pharmacology
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Humans
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Hypertension / drug therapy*
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Hypertension / metabolism
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Hypertension / physiopathology
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Loranthaceae / chemistry*
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Phenols / chemistry*
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Phenols / isolation & purification
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Phenols / pharmacology
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Plants, Medicinal / chemistry
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Pyrones / chemistry*
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Pyrones / isolation & purification
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Pyrones / pharmacology
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Rats
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Tissue Culture Techniques
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Vasodilator Agents / chemistry*
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Vasodilator Agents / isolation & purification
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Vasodilator Agents / pharmacology
Substances
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Antihypertensive Agents
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Biological Products
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Calcium Channels, L-Type
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Carbonic Anhydrase Inhibitors
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Phenols
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Pyrones
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Vasodilator Agents
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dodoneine
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Carbonic Anhydrase III