[en] The emergence of artemisinin-resistant parasites in Africa highlights the need to expand the arsenal of new antimalarial lead pharmacophores with good pharmacological properties and novel mechanisms of action, particularly those derived from natural products. Lantana camara L. is a medicinal plant historically used to treat various ailments, including malaria. Decoctions of its leaves and roots have traditionally been used in endemic regions to treat the disease. However, a thorough validation of its efficacy through the identification of its antimalarial chemical pharmacophores has never been achieved. The purpose of this study was to unveil antiplasmodial chemical “hits” from the leaves and roots of L. camara coupled with in silico predictions of their pharmacokinetic properties and drug-likeness. Crude ethanolic and EtOAc-MeOH (12:13; v/v) extracts were obtained through the maceration of L. camara leaves and roots. Subsequently, fractionation was performed, and all fractions were assessed for their activity against chloroquine-susceptible (Pf3D7) and multidrug-resistant (PfDd2) strains of Plasmodium falciparum using the SyBr Green fluorescence-based methods. The antiplasmodial "hit" compounds were isolated through flash silica chromatography followed by successive column chromatography. The obtained compounds were then subjected to in vitro evaluation against the same strains (Pf3D7 and PfDd2). Virtual in silico prediction using an open Artificial Intelligence and Machine Learning (AI/ML)-assisted tool named pKSCM predictor was used to retrieve the pharmacokinetic (ADMET) properties of the potent antiplasmodial scaffolds. The ethanolic leaf and EtOAc-MeOH root extracts of L. camara showed moderate antiplasmodial activity against both chloroquine-sensitive (Pf3D7) and multidrug-resistant (PfDd2) P. falciparum strains. Notably, the RF2 root fraction exhibited significant activity, particularly against PfDd2 (IC₅₀ = 7.73 µg/mL). From this fraction, a binary mixture of furanonaphthoquinones [diodantunezone (1a) and isodiodantunezone (1b) (2:1)] was isolated, showing strong potency against both parasite strains (IC₅₀ = 2.59 µg/mL [12.10 µM] for PfDd2 and 6.05 µg/mL [28.27 µM] for Pf3D7). The compounds were non-toxic to erythrocytes and selective for intraerythrocytic parasites. In silico prediction of ADMET (absorption, distribution, metabolism, and toxicity parameters further supported their drug-like properties. This study provides the first evidence of the antiplasmodial efficacy of L. camara extracts and derivatives, with an emphasis on their drug-like ability, supporting its traditional use against malaria.
Disciplines :
Agriculture & agronomy Chemistry
Author, co-author :
Taguimjeu Tafokeu K, Pierre Leonel ; Université de Liège - ULiège > Département GxABT > Chemistry for Sustainable Food and Environmental Systems (CSFES)
Tchatat Tali, Mariscal Brice
Dongmo, Kevine Johane Jumeta
Fongang, Yannick Stéphane Fotsing
Fauconnier, Marie-Laure ; Université de Liège - ULiège > Département GxABT > Chemistry for Sustainable Food and Environmental Systems (CSFES)
Lenta, Bruno Ndjakou
Boyom, Fabrice Fekam
Sewald, Norbert
Ngouela, Silvère Augustin
Language :
English
Title :
Chemical constituents of the leaves and roots of Lantana camara Linn (Verbenaceae) display good in vitro antiplasmodial potency and ADMET properties
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