Augustamine type alkaloids from Crinum kirkii Alex K. Machocho a , Jaume Bastida b , Carlos Codina b , Francesc Viladomat b , Reto Brun c , Sumesh C. Chhabra a, * a Department of Chemistry, Kenyatta University, PO Box 43844, 00100 GPO, Nairobi, Kenya b Departament de Productes Naturals, Facultat de Farma ` cia, Universitat de Barcelona, Avda. Diagonal 643, E-08028 Barcelona, Spain c Swiss Tropical Institute, Protozoology Laboratory, Socinstraße 57, CH-4002 Basel, Switzerland Received 8 March 2004; received in revised form 17 September 2004 Abstract Sixteen more Amaryllidaceae alkaloids have been isolated from bulbs of Crinum kirkii Baker of which noraugustamine and 4a,N- dedihydronoraugustamine are hitherto unknown. Their structures and those of earlier known alkaloids have been established by physical and spectroscopic analysis. Application of 2D NMR techniques was used for complete characterization of the alkaloids as well as of 3-O-acetylsanguinine. 1,2-Diacetyllycorine and 3-O-acetylsanguinine showed activity against Trypanosoma brucci rhodesiense, the parasite associated with sleeping sickness. 3-O-acetylsanguinine also showed some activity against Trypanosoma cruzi. Ó 2004 Elsevier Ltd. All rights reserved. Keywords: Crinum kirkii; Amaryllidaceae; Alkaloids; Kirkine; Sanguinine; Zephyranthine; 1,2-O-Diacetylzephyranthine; Augustamine; Noraugus- tamine; 4a,N-Dedihydronoraugustamine 1. Introduction Crinum, the largest genus in the subtribe Crininae (Tribe Amaryllideae; Family Amaryllidaceae), has a wide geographical distribution in the temperate and sub- tropical regions (Snijman and Linder, 1996). The mem- bers of the genus have been used in treatment of various ailments and are considered capable of causing dermati- tis (Hutchings et al., 1996). Continuing our phytochem- ical studies of the Amaryllidaceae, the Kenyan Crinum kirkii Baker, a species with a variety of traditional medicinal uses (Kokwaro, 1993; Watt and Breyer- Brandwijk, 1962) was revisited. In the previous study five alkaloids were reported (Bastida et al., 1995). In the present investigation, we describe the characteriza- tion of a further two new alkaloids together with 14 oth- ers already known. The new alkaloids, noraugustamine (1) and 4a,N-dedihydronoraugustamine (2), are related to augustamine, a rare Amaryllidaceae alkaloid that has only been reported once from Crinum augustum Rox (Ali et al., 1983). Lycorine, the main alkaloid, has various biological and pharmacological activities (Bast- ida et al., 1998), and recent reports indicate that it has antimalarial (Campbell et al., 1998), anti-inflammatory (C ¸ itoglu et al., 1998) and antitumour (Yui et al., 1998) activities. Hippadine has been reported to produce reversible inhibition of fertility in male rats (Chattopad- hyay et al., 1983), while 1,2-O-diacetyllycorine exhibited both antimalarial and cytotoxic activity (Campbell et al., 1998). The other main alkaloids were sanguinine, 3-O-acetylsanguinine (3), amabiline and zephyranthine. It was interesting to note high yields of the galanthamine related alkaloids, sanguinine and its acetate (3). 0031-9422/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved. doi:10.1016/j.phytochem.2004.10.004 * Corresponding author. Tel.: +254 20 810901; fax: +254 20 811575. E-mail addresses: scchhabra@avu.org, scchhabra@yahoo.com (S.C. Chhabra). www.elsevier.com/locate/phytochem Phytochemistry 65 (2004) 3143–3149 PHYTOCHEMISTRY