Gigantelline, gigantellinine and gigancrinine, cherylline- and crinine-type alkaloids isolated from Crinum jagus with anti-acetylcholinesterase activity

Three undescribed Amarylidaceae alkaloids, named gigantelline, gigantellinine and gigancrinine, were isolated from Crinum jagus (syn. = Crinum giganteum) collected in Senegal, together with the already known sanguinine, cherylline, lycorine, crinine, flexinine and the isoquinolinone derivative hippadine. Gigantelline, gigantellinine and gigancrinine were characterized as 4-(6,7-dimethoxy-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenol, its 7-O-demethyl-5ꞌ-hydroxy-4ꞌ-methoxy derivative and 5,6a,7,7a,8a,9-hexahydro-6,9a-ethano[1,3]dioxolo[4,5-j]oxireno[2,3-b]phenanthridin-9-ol, respectively, by using spectroscopic (1D and 2D 1H and 13C NMR and HRESIMS) and chemical methods. Their relative configuration was assigned by NOESY NMR spectra and NMR calculations, while the absolute configuration was assigned using electronic circular dichroism (ECD) experiments and calculations. Sanguinine, cherylline, crinine, flexinine, and the isoquinolinone hippadine, were isolated for the first time from C. jagus. Cherylline, gigantellinine, crinine, flexinine and sanguinine inhibited the activity of AChE in a dose-dependent manner, and inhibition by sanguinine was remarkably effective (IC50 = 1.83 ± 0.01 μM). Cherylline and hippadine showed weak cytotoxicity at 100 μM.