New potently bioactive alkaloids from Crinum erubescens

Abstract

Antimalarial bioassay-guided fractionation of the swamp lily Crinum erubescens led to the isolation of four compounds with potent antiplasmodial activity. Compounds 1 and 2 were determined from their spectroscopic data to be the known pesticidal compound cripowellin A and the known pesticidal and antiproliferative compound cripowellin B. 1D and 2D-NMR techniques were used to determine the identities of 3 and 4 as the new compounds cripowellin C and D. A fifth compound was identified as the known alkaloid hippadine, which was inactive against Plasmodium falciparum. The antiplasmodial IC₅₀ values of compounds 1–4 were determined to be 30 ± 2, 180 ± 20, 26 ± 2, and 260 ± 20 nM, respectively, and their antiproliferative IC₅₀ values against the A2780 human ovarian cancer cell line were 11.1 ± 0.4, 16.4 ± 0.1, 25 ± 2, and 28 ± 1 nM.

Introduction

The genus Crinum contains around 110 accepted species with over 270 synonyms belonging to the family Amaryllidaceae.¹ Members of the genus Crinum possess large extravagant flowers on leafless stems and are distributed in moist sites, such as forests, river edges, seasonal pools, or saltpans, and can be found throughout, the tropics of Africa, Asia, America, Southern Africa, Madagascar, and Mascarene and the Pacific Islands.² Extracts from Crinum species have been used traditionally to treat a variety of ailments including fever, pain management, swelling, sores and wounds, cancer, and malaria.³ As a member of the Amaryllidaceae family, the Crinum genus is known to be a rich source of norbelladine type alkaloids, including lycorine, crinine, and narciclasine.⁴ Alkaloids isolated from various Crinum species have shown activity in a wide variety of assays including analgesic, anticancer, antibacterial, antiviral, antifungal, and antimalarial assays.³

Malaria is a tropical disease that has a disproportionate effect in poor and underdeveloped countries without access to western medicine, and with the appearance of artemisinin resistant parasites in five countries there is an urgent need for new and affordable medicines.⁵ Since plants have been a successful source for antimalarial medicines such as quinine and artemisinin, our group has been investigating plant extracts from the Natural Products Discovery Institute (NPDI) collection for new compounds or known compounds with new activity against Plasmodium falciparum.⁶ An extract of Crinum erubescens L. f. ex Aiton displayed strong antimalarial activity from the initial screening and was selected for isolation.