Synthesis and biological evaluation of aconitine-type derivatives as potential cardiotonic agents

Eighteen C19 aconitine-type derivatives were designed and syn­thesized with the modification of core active and strong toxicity components, such as yunaconitine (YA), mesaconitine (MA), and hypaconitine (HA) in Fuzi through hydrolysis and demethylation reactions. Their structures were confirmed by MS,1H NMR and 13C NMR. Isolated frog heart perfusion assay demonstrated that compound 18 exhibited excellent anti-heart failure activity with a cardiotonic rate of 103.14%. Its cardiotonic effect could be completely antagonized by nonselective calcium channel blockers, suggesting that the pharmacological effect of this compound is closely related to the calcium ion influx mechanism.