Identification of Antiprotozoal Compounds from Buxussempervirens L. by PLS-Prediction.

Lara U Szabó,Pascal Mäser,Marcel Kaiser,Thomas J Schmidt

doi:10.3390/molecules26206181

Abstract

Various nor-triterpene alkaloids of Buxus (B.) sempervirens L. have shown remarkable in vitro activity against the causative agents of tropical malaria and East African sleeping sickness. To identify further antiprotozoal compounds of this plant, 20 different fractions of B. sempervirens L., exhibiting a wide range of in vitro bioactivity, were analyzed by UHPLC/+ESI-QqTOF-MS/MS. The analytical profiles were investigated by partial least squares regression (PLS) for correlations between the intensity of LC/MS signals, bioactivity and cytotoxicity. The resulting models highlighted several compounds as mainly responsible for the antiprotozoal activity and thus, worthwhile for subsequent isolation. These compounds were dereplicated based on their mass spectra in comparison with isolated compounds recently reported by us and with literature data. Moreover, an estimation of the cytotoxicity of the highlighted compounds was derived from an additional PLS model in order to identify plant constituents with strong selectivity. In conclusion, high levels of antitrypanosomal and antiplasmodial activity were predicted for eight and four compounds, respectively. These include three hitherto unknown constituents of B. sempervirens L., presumably new natural products.

Highlights

Unicellular eukaryotic (“protozoan”) parasites cause enormous morbidity and mortality [1]
We present partial least squares regression (PLS) models that highlight, besides those already isolated, further alkaloids of B. sempervirens L. with high predicted activity against P. falciparum (Pf) and Trypanosoma brucei rhodesiense (Tbr)
The alkaloid fraction very clearly displayed the highest activity against both pathogens, Pf and Tbr, as well as considerable antiplasmodial selectivity with a selectivity index (SI) of 34

Summary

Introduction

Unicellular eukaryotic (“protozoan”) parasites cause enormous morbidity and mortality [1]. One of the most widespread and serious protozoan diseases is malaria. Malaria is caused by protozoans of the genus Plasmodium (P.), which occur in erythrocytes and in liver parenchyma cells depending on their developmental stage. The disease is transmitted by insect vectors, female Anopheles mosquitos. Several humanpathogenic Plasmodium species (P. falciparum, P. vivax, P. ovale, P. malariae, P. knowlesi and P. cynomolgi) cause different clinical manifestations of the disease.

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Conclusion