[en] After establishment of the pharmacokinetic and toxicological profile of quinine derivatives using in silico approaches, this study reports the synthesis of new acetyl and benzoyl esters of quinine bearing one or more fluorine or chlorine atoms on the acetyl/benzoyl moiety. The antimalarial activity of these compounds on Plasmodium falciparum 3D7 and K1 strains as well as the antiprotozoal activity on Trypanosoma brucei brucei and Trypanosoma cruzi were evaluated. Lastly, the cytotoxicity on MRC-5 SV2 cells was established. The fluoroacetyl ester compounds were found to be more active in vitro against Plasmodium falciparum 3D7 strain than the reference compound quinine. All synthesized quinine derivatives were non-cytotoxic for MRC-5 SV2 cells (CC 50 > 64 µM). These results confirm that the introduction of one or more fluorine atoms into acetyl and benzoyl esters of quinine can sometimes improve the biological activity.
Disciplines :
Pharmacy, pharmacology & toxicology
Author, co-author :
Mvondo Mbala, Jean-Gonfi; Faculty of Sciences, Departement of Chemistry, Université de Kinshasa, Democratic Republic of the Congo
Thierry Mawete, Dani; Faculty of Sciences, Departement of Chemistry, Université de Kinshasa, Democratic Republic of the Congo
Makiese, Alain; Faculty of Sciences, Departement of Chemistry, Université de Kinshasa, Democratic Republic of the Congo
Kwiraviwe, Lwanzo; Laboratoire de Chimie Médicale, Faculty of Pharmaceutical Sciences, Université de Kinshasa, Democratic Republic of the Congo
Pangu, Kuyubuka; Laboratoire de Chimie Médicale, Faculty of Pharmaceutical Sciences, Université de Kinshasa, Democratic Republic of the Congo
Nguimi, Eric; Laboratoire de Chimie Médicale, Faculty of Pharmaceutical Sciences, Université de Kinshasa, Democratic Republic of the Congo
Cimanga Kanyanga, Richard; Laboratoire de Pharmacognosie, Faculty of Pharmaceutical Sciences, Université de Kinshasa, Democratic Republic of the Congo ; Department of Pharmaceutical Sciences, Natural Products & Food Research and Analysis (NaturA), University of Antwerp, Anvers, Belgium
Pieters, Luc; Department of Pharmaceutical Sciences, Natural Products & Food Research and Analysis (NaturA), University of Antwerp, Anvers, Belgium
Degotte, Gilles ; Université de Liège - ULiège > Unités de recherche interfacultaires > Centre Interdisciplinaire de Recherche sur le Médicament (CIRM)
Frederich, Michel ; Université de Liège - ULiège > Département de pharmacie > Pharmacognosie
Matondo, Aristote; Faculty of Sciences, Departement of Chemistry, Université de Kinshasa, Democratic Republic of the Congo
Van Pelt, Natascha; Laboratory of Microbiology, Parasitology and Hygiene (LMPH), Infla-Med Centre of Excellence, University of Antwerp, Antwerp, Belgium
Caljon, Guy; Laboratory of Microbiology, Parasitology and Hygiene (LMPH), Infla-Med Centre of Excellence, University of Antwerp, Antwerp, Belgium
Pirotte, Bernard ; Université de Liège - ULiège > Département de pharmacie
Mbala Mavinga, Blaise; Faculty of Sciences, Departement of Chemistry, Université de Kinshasa, Democratic Republic of the Congo
Bambi-Nyanguile, Sylvie-Mireille; Laboratoire de Chimie Médicale, Faculty of Pharmaceutical Sciences, Université de Kinshasa, Democratic Republic of the Congo
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