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

Research Article Volume 7 Issue 2

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 Guillon1*, Anita Cohen2, Sarah Monic1,3, Clotilde Boudot4, Solène Savrimoutou1, Sandra Albenque-Rubio1, Stéphane Moreau1, Alexandra Dassonville-Klimpt5, Jean-Louis Mergny6, Luisa Ronga7, Mikel Bernabeu de Maria7, Nikita Tyurin-Schmitt1, Paul Parrens1, Adrien Labarthe1, Valentin Gomez1, Serge Moukha8,9, Pascale Dozolme8,9, Nadine Azas2, Valérie Gabelica10, Patrice Agnamey5, Céline Damiani5,11, Anne Totet5,11, Catherine Mullié5, Bertrand Courtioux4 and Pascal Sonnet5

1University of Bordeaux, Faculty of Pharmacy, CNRS, INSERM, ARNA, UMR 5320, U1212, France
2University of Aix-Marseille, IRD, AP-HM, SSA, VITROME, Marseille, France
3Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QW, United Kingdom
4University of Limoges, INSERM U1094, Tropical Neuroepidemiology, Limoges, France and Institute of Neuroepidemiology and Tropical Neurology, France
5University of Picardie Jules Verne, Agents Infectieux, Résistance et Chimiothérapie (AGIR), UR 4294, UFR de Pharmacie, France
6Ecole Polytechnique, Laboratoire d’Optique et Biosciences, CNRS, INSERM, Institut Polytechnique de Paris, France
7Université de Pau et des Pays de l'Adour, E2S UPPA, CNRS, IPREM, France
8Centre de Recherche Cardio-thoracique de Bordeaux (CRCTB), UMR U1045 INSERM, PTIB - Hôpital Xavier Arnozan, France
9INRAE Bordeaux Aquitaine, F- 33140 Villenave-d'Ornon, France
10University of Bordeaux, IECB, CNRS, INSERM, ARNA, France
11Laboratoire de Parasitologie-Mycologie, Centre de Biologie Humaine, CHU Amiens-Picardie, France

*Corresponding Author: Jean Guillon, University of Bordeaux, Faculty of Pharmacy, CNRS, INSERM, ARNA, UMR 5320, U1212, France.

Received: January 07, 2023; Published: January 27, 2023


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 mM 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 M. 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.

Keywords: Phenanthroline; G-quadruplex; Antimalarial Activity; Antileishmanial Activity; Antitrypanosomal Activity


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Citation: Jean Guillon., 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 7.2 (2023): 50-65.


Copyright: © 2022 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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