Article Dans Une Revue Acta Scientific Pharmaceutical Sciences Année : 2023

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

Rabindra Nath Das
  • Fonction : Auteur
Anita Cohen
  • Fonction : Auteur
Clotilde Boudot
  • Fonction : Auteur
Solène Savrimoutou
  • Fonction : Auteur
Sandra Albenque-Rubio
  • Fonction : Auteur
Stéphane Moreau
  • Fonction : Auteur
Jean-Louis Mergny
  • Fonction : Auteur
Luisa Ronga
Ioannis Kanavos
Charles Descamps
  • Fonction : Auteur
Valentin Verdier
  • Fonction : Auteur
Bertrand Courtioux
Jean Guillon
  • Fonction : Auteur

Résumé

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 IC 50 values in the sub and μM 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.

Dates et versions

hal-04552497 , version 1 (19-04-2024)

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Citer

Rabindra Nath Das, Anita Cohen, Clotilde Boudot, Solène Savrimoutou, Sandra Albenque-Rubio, 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, 2023, 7 (7), pp.15-33. ⟨10.31080/ASPS.2023.07.0965⟩. ⟨hal-04552497⟩
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