Isolation and biological activity of alkaloids from Vinca minor L. related to Alzheimerʼs disease

Natural products, especially alkaloids, are still a substantial resource for the drug development [1]. Based on the preliminary screening of alkaloidal extracts of various plants against Alzheimerʼs disease, Vinca minor L. (Apocynaceae) have been chosen for a detailed phytochemical and biological study. V. minor L. is an evergreen trailing subshrub common in Europe with rich content of monoterpene indole alkaloids [2]. In this study, we have isolated and identified active alkaloidal compounds and assessed their potential to inhibit hAChE, hBuChE, POP, and GSK-3β – enzymes that play a key role in the pathophysiology of Alzheimerʼs disease. Using chromatographic methods, we have isolated 23 alkaloids; 11 of them have been reported in this species for the first time. One alkaloidal structure was undescribed and was named as vincaminorudeine. The most active compound was (−)-2-ethyl-3[2-(3-ethylpiperidinyl)-ethyl]-1H-indole with IC₅₀ = 0.65 µM for the inhibition of hBuChE, and with IC₅₀ = 58 µM for the inhibition of POP. Other alkaloids that exhibited significant inhibition against hBuChE (IC₅₀ < 30 µM) were vincaminoreine, minovine, 16-methoxyminovine, vincorine, and tubotaiwine. None of the isolated alkaloids was active against hAChE. The (−)-2-ethyl-3[2-(3-ethylpiperidinyl)-ethyl]-1H-indole was also further studied for its pharmacokinetic, revealing a reversible competitive type of inhibition for hBuChE with Ki = 55 nM. This compound can also penetrate the blood-brain barrier by passive diffusion, as was assessed by the PAMPA study. Additionally, the alkaloid on the panel of ten cell lines showed non-cytotoxicity. These compelling results open a possibility for further research on this indole alkaloid.

• References

• 1 Newman DJ, Cragg GM. Natural Products as Sources of New Drugs from 1981 to 2014. J Nat Prod 2016; 79: 629-661
• 2 Khanavi M, Pourmoslemi S, Farahanikia B. et al. Cytotoxicity of Vinca minor. Pharm Biol 2010; 48: 96-100

Publication History

Article published online:
12 December 2022