New lycorine-type alkaloid from Lycoris traubii and evaluation of antitrypanosomal and antimalarial activities of lycorine derivatives

• Published in: Bioorganic & medicinal chemistry 2008-12, Vol.16 (24), p.10182-10189
• Main Authors: Toriizuka, Yosuke, Kinoshita, Eri, Kogure, Noriyuki, Kitajima, Mariko, Ishiyama, Aki, Otoguro, Kazuhiko, Yamada, Haruki, Ōmura, Satoshi, Takayama, Hiromitsu
• Format: Article
• Language: English
• Subjects: Alkaloid; Alkaloids - chemistry; Alkaloids - isolation & purification; Alkaloids - pharmacology; Amaryllidaceae; Amaryllidaceae Alkaloids - chemistry; Amaryllidaceae Alkaloids - isolation & purification; Animals; Antimalarial activity; Antimalarials - chemistry; Antimalarials - isolation & purification; Antimalarials - pharmacology; Antitrypanosomal activity; Biological and medical sciences; General pharmacology; Inhibitory Concentration 50; Liliaceae - chemistry; Lycorine; Lycoris; Medical sciences; Parasitic Sensitivity Tests; Pharmacognosy. Homeopathy. Health food; Pharmacology. Drug treatments; Phenanthridines - chemistry; Phenanthridines - isolation & purification; Plasmodium falciparum; Plasmodium falciparum - drug effects; Structure elucidation; Structure–activity relationship; Trypanocidal Agents - chemistry; Trypanocidal Agents - isolation & purification; Trypanocidal Agents - pharmacology; Trypanosoma brucei brucei
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2008.10.061

A new lycorine derivative LT1 ( 4) was isolated from the Lycoris traubii Hayward (Amaryllidaceae). Some lycorine ester derivatives were examined for their inhibitory activity against trypanosoma and against malaria in vitro. Among them, 6 showed potent activity against trypanosoma and 4, 8, 11, and 12 showed significant activity against malaria. A new lycorine derivative LT1 ( 4) was isolated from the aerial part and bulbs of Lycoris traubii Hayward (Amaryllidaceae). Its structure including absolute configuration was established by spectroscopic analysis and semi-synthesis to be 1- O-(3′ S)-hydroxybutanoyllycorine. Some lycorine ester derivatives including LT1 were examined for their inhibitory activity against Trypanosoma brucei brucei, the parasite associated with sleeping sickness, and against Plasmodium falciparum, the causative agent of malaria. Among them, 2- O-acetyllycorine ( 6) showed the most potent activity against parasitic T. b. brucei, and LT1 ( 4), 1- O-(3′ R)-hydroxybutanoyllycorine ( 8), 1,2-di- O-butanoyllycorine ( 11), and 1- O-propanoyllycorine ( 12) showed significant activity against P. falciparum in an in vitro experiment.