RESUMEN
The cardiac effect of thirty-eight diterpenoid alkaloids was evaluated on the isolated bullfrog heart model. Among them, twelve compounds exhibited appreciable cardiac activity, with compounds 3 and 35 being more active than the reference drug lanatoside. The structure-cardiac activity relationships of the diterpenoid alkaloids were summarized based on our present and previous studies [2]: i) 1α-OMe or 1α-OH, 8-OH, 14-OH, and NH (or NMe) are key structural features important for the cardiac effect of the aconitine-type C19-diterpenoid alkaloids without any esters. C18-diterpenoid alkaloids, lycoctonine-type C19-diterpenoid alkaloids, and the veatchine- and denudatine-type C20-diterpenoid alkaloids did not show any cardiac activity; ii) the presence of 3α-OH is beneficial to the cardiac activity; iii) the effect on the cardiac action of 6α-OMe, 13-OH, 15α-OH, and 16-demethoxy or a double bond between C-15 and C-16 depends on the substituent pattern on the nitrogen atom.
Asunto(s)
Alcaloides/farmacología , Fármacos Cardiovasculares/farmacología , Diterpenos/farmacología , Corazón/efectos de los fármacos , Alcaloides/química , Animales , Fármacos Cardiovasculares/química , Diterpenos/química , Estructura Molecular , Rana catesbeiana , Relación Estructura-ActividadRESUMEN
On the basis of intensive interpretation of the 1H NMR spectroscopic data, the ring A conformation of aconine (1) was speculated as twist boat in CDCl3, and as chair or twist boat in acetone-d6 and pyridine-d5. The ring A of pseudaconine (2) adopts the chair conformation in CDCl3, acetone-d6, and pyridine-ds. Accordingly, the boat conformation of ring A in these two diterpenoid alkaloids in CDCl3 reported in the literature [1] should be revised. The difference in 13C NMR data for the same compound (1 or 2) in two different solvents (CDCl3, pyridine-d5) can be attributed to solvent effects.