Integration of dereplication and regression analysis for rapid characterization of antiplasmodial compounds from the leaves of Combretum paniculatum

Abstract

The rapid development of modern analytical techniques and various chemometric approaches provide new perspectives for early metabolite identification in natural products research. These techniques represent a potential strategy to streamline the traditional and laborious process of isolating natural products through targeting of unknown active compounds before purification. In the present study, these innovative techniques have been applied on extracts of the leaves of Combretum paniculatum, which have demonstrated promising antiplasmodial activity during our preliminary studies, leading to a quick and effective identification of compounds correlated to this activity. The fractionation of crude extracts was carried out, followed by multivariate data analysis of liquid chromatography–high resolution mass spectrometry (LC–HRMS) profiles of the fractions obtained. In parallel, all fractions were screened against Plasmodium falciparum strain K1, and their cytotoxicity against MRC-5 cells was determined. Dereplication studies combining UPLC-MS/MS-based molecular networking, in silico analysis and NMR methods were employed to identify the important metabolites. Several compounds strongly correlated with antiplasmodial activity have been identified. Six compounds including rutin (IC50 6.7 µM) and foliasalacioside F (IC50 10.6 µM ) have been isolated and their OPLS predicted score values were in agreement with antiplasmodial results found in vitro. These preliminary results provided clear evidence on the effectiveness of using these innovative methods (chemometrics and dereplication analysis) for the rapid identification of active metabolites in plant extracts. Further research aiming for the isolation of additional promising compounds which have shown a strong correlation with antiplasmodial activity is ongoing.