Acta Scientific Pharmaceutical Sciences (ASPS)(ISSN: 2581-5423)

Research Article Volume 7 Issue 7

Development, Synthesis and Antiprotozoal Assessment of New Substituted Diquinolinyl-Pyridine Derivatives as Antiparasitic Agents by Potential G-4 Binding

Rabindra Nath Das1,2, Anita Cohen3, Clotilde Boudot4, Solène Savrimoutou1, Sandra Albenque-Rubio1, Stéphane Moreau1, Jean-Louis Mergny5, Luisa Ronga6, Ioannis Kanavos6, Charles Descamps1, Valentin Verdier1, Patrice Agnamey7, Catherine Mullié7, Bertrand Courtioux4, Pascal Sonnet7 and Jean Guillon1*

1University of Bordeaux, Faculty of Pharmacy, CNRS, INSERM, ARNA, France
2Department of Chemistry, College of Engineering and Technology, Kattankulathur – Chennai, Tamil Nadu, India
3University of Aix-Marseille, IRD, AP-HM, SSA, VITROME, France
4University of Limoges, INSERM U1094, Tropical Neuroepidemiology, Limoges, France; Institute of Neuroepidemiology and Tropical Neurology, France
5Ecole Polytechnique, Laboratoire d’Optique et Biosciences, CNRS, INSERM, Institut Polytechnique de Paris, France
6Université de Pau et des Pays de l'Adour, E2S UPPA, CNRS, IPREM, France
7University of Picardie Jules Verne, Agents Infectieux, Résistance et Chimiothérapie (AGIR), UR 4294, UFR de Pharmacie, France

*Corresponding Author: AJean Guillon, University of Bordeaux, Faculty of Pharmacy, CNRS, INSERM, ARNA, France.

Received: May 16, 2023; Published: June 23, 2023


In order to fight malaria, a public health problem for which nearly half of the world’s population is at risk and responsible a life-threatening disease primarily found in tropical countries and for which the estimated number of deaths stood at 619 000 in 2021, an original strategy is to design and synthesize quinoline-based drugs that are not recognized by the protein system involved in the drug efflux. Thus, a series of new 2,6-di-(carbamoyl-2-quinolinyl)pyridine derivatives was considered, synthesized, and evaluated in vitro against three parasites (Plasmodium falciparum, Leishmania donovani and Trypanosoma brucei brucei). Pharmacological results showed antiparasitic activity with IC50 values in the sub and mM range. The in vitro cytotoxicity of these new diquinolinyl-pyridine derivatives was evaluated on human HepG2 cells. The diquinolinyl-pyridine 1e was found as the most potent antimalarial candidate with a ratio of cytotoxic to antiprotozoal activities of 73.5 against the P. falciparum CQ-resistant strain W2. Moreover, derivative 3b was also identified as the most potent antiparasitic compound with a selectivity index (SI) of 21.48 on 3D7 P. falciparum CQ-sensitive strain. In addition, the 2,6-di-(carbamoyl-2-quinolinyl)pyridines 2c and 3b were also identified as the most interesting antitrypanosomal candidate drugs with selectivity index (SI) of 75.9 and 38.94, respectively on T. brucei brucei strain. It has been previously described that the telomeres of parasites P. falciparum and Trypanosoma could be considered as potential targets of this kind of nitrogen heterocycles, thus the ability of these new derivatives to stabilize the parasitic telomeric G-quadruplexes have been measured through a FRET melting assay.

 Keywords: Diquinolinyl-pyridine; Antimalarial Activity; Antileishmanial Activity; Antitrypanosomal Activity; G-quadruplex.


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Citation: Jean Guillon., et al. “Development, Synthesis and Antiprotozoal Assessment of New Substituted Diquinolinyl-Pyridine Derivatives as Antiparasitic Agents by Potential G-4 Binding". Acta Scientific Pharmaceutical Sciences 7.7 (2023): 15-33.


Copyright: © 2023 Jean Guillon., et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


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