Further Studies on Structure-Cardiac Activity Relationships of Diterpenoid Alkaloids

Abstract

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) 1-OMe or 1-OH, 8-OH, 14-OH, and NH (or NMe) are key structural features important for the cardiac effect of the aconitine-type C 19-diterpenoid alkaloids without any esters. C 18-diterpenoid alkaloids, lycoctoninetype C 19-diterpenoid alkaloids, and the veatchine-and denudatine-type C 20-diterpenoid alkaloids did not show any cardiac activity; ii) the presence of 3-OH is beneficial to the cardiac activity; iii) the effect on the cardiac action of 6-OMe, 13-OH, 15-OH, and 16-demethoxy or a double bond between C-15 and C-16 depends on the substituent pattern on the nitrogen atom.

Antifungal Activity of New Diterpenoid Alkaloids Isolated by Different Chromatographic Methods from Delphinium peregrinum L. var. eriocarpum Boiss

“…The 13 C-NMR spectrum of Delcarpum ( 1 ) contained only three signals up field from 81 ppm at δ C 32.8 (C-4), 47.6 (C-11), and 80.8 ppm (C-8) indicating the compound possessing is an aconitine-type C- 19 diterpenoid alkaloids with a tertiary methoxy group at C-8 at δ C 48.6 ( q ) [ 4 ].…”

“…Delphinium is a medical herb used for the treatment of epilepsy, neurotoxic, and asthma [ 2 , 3 ]. The Delphinium alkaloids are currently under investigation in search for new analgesic, antiinflammatory drugs, muscular relaxation, anticonvulsant, pyramis lesion, and cardiac effects [ 3 , 4 , 5 ]. Moreover, a certain number of natural diterpenoid alkaloids have been reported to possess antiproliferative activities against various human cancer cell lines, indicating their great potential as new drugs for treating the corresponding cancers [ 6 , 7 ].…”

On the Famous Traditional Chinese Medicine “Fu Zi”: Discovery, Research, and Development of Cardioactive Constituent Mesaconine

“…An in-depth study in 2015 further revealed that, in addition to the ester group-containing aconitine-type alkaloids, the lycoctonine-type and C 20 -diterpenoid alkaloids had no cardiac activities. It was also noted that the hydrobromide salt of mesaconine ( 11 ) was ineffective in the isolated bullfrog hearts test [ 15 ], but it exhibited positive in vivo activity in rats, despite a slower onset of drug action than the free base mesaconine [ 16 ].…”

“…4). In summary, the key features of the production process included [16], which we accidentally discovered in 1999 [18].…”

Diterpenoid Alkaloids from Delphinium aemulans

“…The genus Delphinium belongs to the Ranunculaceae family, comprising of approximately 300 species, is widely distributed in the temperate regions of the northern hemisphere, of which 113 are Chinese endemic species [1]. Previous chemical and pharmacological studies have shown that diterpenoid alkaloids are the main active constituents of this genus, which are highly oxygenated and complex natural products with various biological activities, such as anti-inflammatory, analgesic, anti-arrhythmia, cardioactive, antitumor, antifungal, as well as insecticidal and antifeedant activities [2][3][4][5].…”