Antiprotozoal Activity of Buxus sempervirens and Activity-Guided Isolation of O-tigloylcyclovirobuxeine-B as the Main Constituent Active against Plasmodium falciparum ‡

Molecules

Julia B. Althaus²  Gerold Jerz¹  Peter Winterhalter¹  Marcel Kaiser³  Reto Brun³ 

[1] Institut für Lebensmittelchemie, Technische Universität Braunschweig, Schleinitzstraße 20, D-38106 Braunschweig, Germany; E-Mails:;Institut für Pharmazeutische Biologie und Phytochemie (IPBP), University of Münster, Pharma Campus, Corrensstraße 48, D-48149 Münster, Germany; E-Mail:;Tropical and Public Health Institute (Swiss TPH), Socinstraße 57, CH-4002 Basel, Switzerland; E-Mails:

关键词: Buxus sempervirens;    antiprotozoal activity;    cycloartane alkaloids;    Plasmodium falciparum;    Trypanosoma brucei rhodesiense;    Trypanosoma cruzi;    Leishmania donovani;    spiral-coil countercurrent chromatography;   

DOI  :  10.3390/molecules19056184

来源: mdpi

【 摘 要 】

Buxus sempervirens L. (European Box, Buxaceae) has been used in ethnomedicine to treat malaria. In the course of our screening of plant extracts for antiprotozoal activity, a CH₂Cl₂ extract from leaves of B. sempervirens showed selective in vitro activity against Plasmodium falciparum (IC₅₀ = 2.79 vs. 20.2 µg/mL for cytotoxicity against L6 rat cells). Separation of the extract by acid/base extraction into a basic and a neutral non-polar fraction led to a much more active and even more selective fraction with alkaloids while the fraction of non-polar neutral constituents was markedly less active than the crude extract. Thus, the activity of the crude extract could clearly be attributed to alkaloid constituents. Identification of the main triterpene-alkaloids and characterization of the complex pattern of this alkaloid fraction was performed by UHPLC/+ESI-QTOF-MS analyses. ESI-MS/MS target-guided larger scale preparative separation of the alkaloid fraction was performed by ‘spiral coil-countercurrent chromatography’. From the most active subfraction, the cycloartane alkaloid O-tigloylcyclovirobuxeine-B was isolated and evaluated for antiplasmodial activity which yielded an IC₅₀ of 0.455 µg/mL (cytotoxicity against L6 rat cells: IC₅₀ = 9.38 µg/mL). O-tigloylcyclovirobuxeine-B is thus most significantly responsible for the high potency of the crude extract.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.