Article Dans Une Revue Acta Scientific Pharmaceutical Sciences Année : 2023

Synthesis and Antiprotozoal Evaluation of New 2,9-bis[(pyridinylalkylaminomethyl) phenyl]-1,10-Phenanthroline Derivatives by Targeting G-quadruplex, an Interesting Pharmacophore Against Drug Efflux

Jean Guillon
  • Fonction : Auteur
Anita Cohen
  • Fonction : Auteur
Sarah Monic
  • 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
Mikel Bernabeu de Maria
  • Fonction : Auteur
Nikita Tyurin-Schmitt
  • Fonction : Auteur
Paul Parrens
  • Fonction : Auteur
Adrien Labarthe
  • Fonction : Auteur
Valentin Gomez
  • Fonction : Auteur
Serge Moukha
  • Fonction : Auteur
  • PersonId : 1413106
  • IdHAL : smoukha
Pascale Dozolme
Nadine Azas
  • Fonction : Auteur
Valérie Gabelica
  • Fonction : Auteur
Bertrand Courtioux

Résumé

A series of new 2,9-bis[(pyridinylalkylaminomethyl)phenyl]-1,10-phenanthroline compounds 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 µM range. The in vitro cytotoxicity of these novel aza derivatives was evaluated on human HepG2 cells. The phenanthroline 1f was noticed as the most potent antimalarial candidate with a ratio of cytotoxic to antiprotozoal activities of 912.4 against the P. falciparum CQ-resistant strain W2. In addition, the phenanthroline 1a was also identified as the most potent antiparasitic derivative with a selectivity index (SI) of 811.8 on P. falciparum CQ-sensitive strain 3D7. Against the promastigote forms of L. donovani, the same phenanthroline 1a was found the most active compounds with an IC50 of 2.08 mM. In addition, the phenanthrolines 1f and 1i were also identified as the most promising trypanosomal candidates with selectivity index (SI) of 231.1 and 143.7, respectively on T. brucei brucei strain. As the telomeres of the parasites P. falciparum and Trypanosoma could be considered as possible targets of this kind of aza heterocyclic molecules, their ability to stabilize the parasitic telomeric G-quadruplexes have been measured through the FRET melting assay.

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hal-04558862 , version 1 (25-04-2024)

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Jean Guillon, Anita Cohen, Sarah Monic, Clotilde Boudot, Solène Savrimoutou, et al.. Synthesis and Antiprotozoal Evaluation of New 2,9-bis[(pyridinylalkylaminomethyl) phenyl]-1,10-Phenanthroline Derivatives by Targeting G-quadruplex, an Interesting Pharmacophore Against Drug Efflux. Acta Scientific Pharmaceutical Sciences, 2023, 7 (2), pp.50-65. ⟨10.31080/asps.2023.07.0934⟩. ⟨hal-04558862⟩
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