Unveiling antiplasmodial alkaloids from a cumulative collection of Strychnos extracts by multi-informative molecular networks

Olivier Bonnet; Mehdi A Beniddir; Pierre Champy; Gilles Degotte; Lúcia Mamede; Pauline Desdemoustier; Allison Ledoux; Alembert Tiabou Tchinda; Luc Angenot; Michel Frédérich

doi:10.3389/fmolb.2022.967012

Unveiling antiplasmodial alkaloids from a cumulative collection of Strychnos extracts by multi-informative molecular networks

Front Mol Biosci. 2022 Sep 26:9:967012. doi: 10.3389/fmolb.2022.967012. eCollection 2022.

Affiliations

¹ Laboratory of Pharmacognosy, Center of Interdisciplinary Research on Medicines (CIRM), University of Liege, Liege, Belgium.
² Équipe "Chimie des Substances Naturelles" BioCIS, CNRS, Université Paris-Saclay, Châtenay-Malabry, France.
³ Institute of Medical Research and Medicinal Plants Studies (IMPM), Yaoundé, Cameroon.

Abstract

Malaria, a disease known for thousands of years and caused by parasites of the Plasmodium genus, continues to cause many deaths throughout the world today, particularly due to the emergence of parasite resistance to the current therapeutic arsenal. Plants of the Strychnos genus, remarkable due to their multiple traditional uses as well as their alkaloid content, are promising candidates to develop new antimalarial treatments. Indeed, previous research on this plant group has shown promising (≤ 5 µg/ml) or good (between 5 and 15 µg/ml) antiplasmodial activities. Using the chloroquine-sensitive strain of Plasmodium falciparum (3D7), and artemisinin as positive control, a screening of antiplasmodial activities from 43 crude methanolic extracts from 28 species of the Strychnos genus was carried out in three independent assays. A total of 12 extracts had good (6 extracts) or promising (6 extracts) antiplasmodial activities. These results allowed both to confirm known activities but also to detect new ones. These extracts were then analyzed by HPLC-ESI(+)-Q/TOF, and the processed MS/MS data allowed to generate a molecular network in which the antiplasmodial activities were implemented as metadata. The exploration of the molecular network revealed the presence of alkaloids still unknown, and potentially active against malaria, in particular alkaloids close to usambarensine and its derivatives. This study shows that the emergence of molecular networking offers new leads for identifications of alkaloids from the Strychnos genus. The presence of unknown alkaloids potentially active against malaria confirms all the interest to continue in studying the Strychnos genus. Bioassay- and mass-guided fractionations as well as various dereplication tools would allow to identify and characterize these interesting alkaloids further.

Keywords: Loganiaceae; Strychnos; antiplasmodial; chemoinformatics; malaria; mass spectrometry; metabolomics; molecular networking.