Uncovering the antimalarial potential of toad venoms through a bioassay-guided fractionation process.

Bufadienolide; Malaria; Rhinella marina; Separative techniques; Toad venom; Amphibian Venoms; Antimalarials; Plant Extracts; Animals; Plasmodium falciparum; Bufonidae; Plant Extracts/chemistry; Amphibian Venoms/chemistry; Amphibian Venoms/therapeutic use; Antimalarials/therapeutic use; Malaria/drug therapy; Parasitology; Infectious Diseases; Pharmacology (medical); Pharmacology

Abstract :

[en] Malaria remains to date one of the most devastating parasitic diseases worldwide. The fight against this disease is rendered more difficult by the emergence and spread of drug-resistant strains. The need for new therapeutic candidates is now greater than ever. In this study, we investigated the antiplasmodial potential of toad venoms. The wide array of bioactive compounds present in Bufonidae venoms has allowed researchers to consider many potential therapeutic applications, especially for cancers and infectious diseases. We focused on small molecules, namely bufadienolides, found in the venom of Rhinella marina (L.). The developed bio-guided fractionation process includes a four solvent-system extraction followed by fractionation using flash chromatography. Sub-fractions were obtained through preparative TLC. All samples were characterized using chromatographic and spectrometric techniques and then underwent testing on in vitro Plasmodium falciparum cultures. Two strains were considered: 3D7 (chloroquine-sensitive) and W2 (chloroquine-resistant). This strategy highlighted a promising activity for one compound named resibufogenin. With IC50 values of (29 ± 8) μg/mL and (23 ± 1) μg/mL for 3D7 and W2 respectively, this makes it an interesting candidate for further investigation. A molecular modelling approach proposed a potential binding mode of resibufogenin to Plasmodium falciparum adenine-triphosphate 4 pump as antimalarial drug target.

Disciplines :

Chemistry

Author, co-author :

Wells, Mathilde ; Université de Mons - UMONS > Faculté de Médecine et de Pharmacie > Service d'Analyse pharmaceutique

Fossepre, Mathieu ; Université de Mons - UMONS

Hambye, Stéphanie; Laboratory of Pharmaceutical Analysis, Faculty of Medicine and Pharmacy, Research Institute for Health Sciences and Technology, University of Mons - UMONS, Place du Parc 20, 7000, Mons, Belgium

Surin, Mathieu ; Université de Mons - UMONS > Faculté des Sciences > Service de Chimie des matériaux nouveaux

Blankert, Bertrand ; Université de Mons - UMONS

Language :

English

Title :

Uncovering the antimalarial potential of toad venoms through a bioassay-guided fractionation process.

Publication date :

December 2022

Journal title :

International Journal for Parasitology: Drugs and Drug Resistance

ISSN :

2211-3207

Publisher :

Elsevier Ltd, Netherlands

Volume :

Pages :

97 - 107

Peer reviewed :

Peer Reviewed verified by ORBi

Additional URL :

https://api.elsevier.com/content/article/PII:S2211320722000227?httpAccept=text/xml

Research unit :

Chemistry of Novel Materials
M130 - Analyse pharmaceutique

Research institute :

Research Institute for Health Sciences and Technology

Funding text :

The authors warmly acknowledge Prof. Pierre Duez and his team for their expertise and kindly sharing their equipment. The authors also wish to thank Prof. Pascal Gerbaux and Irène Semay for their help during MS analysis, Dr Céline Hénoumont for her assistance for generating NMR data and Prof. Carmen Burtea for giving us access to her laboratory's equipment. The University of Mons is also acknowledged for the funding a full PhD grant for Mathilde Wells. M.F. and M.S. thank FNRS- FWO Excellence of Science project PRECISION (Grant No 30650939 ). Computational resources have been provided by the Consortium des Équipements de Calcul Intensif (CÉCI), funded by FNRS (Grant No. 2.5020.11 ) and by the Wallonia Region.The authors warmly acknowledge Prof. Pierre Duez and his team for their expertise and kindly sharing their equipment. The authors also wish to thank Prof. Pascal Gerbaux and Irène Semay for their help during MS analysis, Dr Céline Hénoumont for her assistance for generating NMR data and Prof. Carmen Burtea for giving us access to her laboratory's equipment. The University of Mons is also acknowledged for the funding a full PhD grant for Mathilde Wells. M.F. and M.S. thank FNRS-FWO Excellence of Science project PRECISION (Grant No 30650939). Computational resources have been provided by the Consortium des Équipements de Calcul Intensif (CÉCI), funded by FNRS (Grant No. 2.5020.11) and by the Wallonia Region.

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since 09 January 2023

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