Design, synthesis, and antiprotozoal evaluation of new 2,4-bis[(substituted-aminomethyl)phenyl]quinoline, 1,3-bis[(substituted-aminomethyl)phenyl]isoquinoline and 2,4-bis[(substituted-aminomethyl)phenyl]quinazoline derivatives

Jean Guillon; Anita Cohen; Clotilde Boudot; Alessandra Valle; Vittoria Milano; Rabindra Nath Das; Aurore Guédin; Stéphane Moreau; Luisa Ronga; Solène Savrimoutou; Maxime Demourgues; Elodie Reviriego; Sandra Rubio; Sandie Ferriez; Patrice Agnamey; Cécile Pauc; Serge Moukha; Pascale Dozolme; Sophie da Nascimento; Pierre Laumaille; Anne Bouchut; Nadine Azas; Jean-Louis Mergny; Catherine Mullié; Pascal Sonnet; Bertrand Courtioux

doi:10.1080/14756366.2019.1706502

Article dans une revue

Design, synthesis, and antiprotozoal evaluation of new 2,4-bis[(substituted-aminomethyl)phenyl]quinoline, 1,3-bis[(substituted-aminomethyl)phenyl]isoquinoline and 2,4-bis[(substituted-aminomethyl)phenyl]quinazoline derivatives

Jean Guillon ^{1, *} Anita Cohen ² Clotilde Boudot ³ Alessandra Valle ¹ Vittoria Milano ¹ Rabindra Nath Das ¹ Aurore Guédin ¹ Stéphane Moreau ¹ Luisa Ronga ^{4, 5} Solène Savrimoutou ⁴ Maxime Demourgues ¹ Elodie Reviriego ¹ Sandra Rubio ¹ Sandie Ferriez ¹ Patrice Agnamey ⁶ Cécile Pauc ⁶ Serge Moukha ⁷ Pascale Dozolme ⁷ Sophie da Nascimento ⁸ Pierre Laumaille ⁹ Anne Bouchut ⁹ Nadine Azas ² Jean-Louis Mergny ⁴ Catherine Mullié ⁹ Pascal Sonnet ⁹ Bertrand Courtioux ^{10, 3}

* Auteur correspondant

1 ARNA - Acides Nucléiques : Régulations Naturelle et Artificielle

2 VITROME - Vecteurs - Infections tropicales et méditerranéennes

3 NET - Neuroépidémiologie Tropicale

4 ARNA - Régulations Naturelles et Artificielles

5 IPREM - Institut des sciences analytiques et de physico-chimie pour l'environnement et les materiaux

6 AGIR - Agents infectieux, résistance et chimiothérapie - UR UPJV 4294

7 UFR des Sciences Pharmaceutiques

8 LG - Laboratoire des Glucides

9 LG2A - Laboratoire de Glycochimie, des Antimicrobiens et des Agro-ressources - UMR CNRS 7378

10 UNILIM - Université de Limoges

Abstract : A series of new 2,4-bis[(substituted-aminomethyl)phenyl]quinoline, 1,3-bis[(substituted-aminomethyl)phenyl]isoquinoline, and 2,4-bis[(substituted-aminomethyl)phenyl]quinazoline derivatives was designed, synthesised, and evaluated in vitro against three protozoan parasites (Plasmodium falciparum, Leishmania donovani, and Trypanosoma brucei brucei). Biological results showed antiprotozoal activity with IC50 values in the µM range. In addition, the in vitro cytotoxicity of these original molecules was assessed with human HepG2 cells. The quinoline 1c was identified as the most potent antimalarial candidate with a ratio of cytotoxic to antiparasitic activities of 97 against the P. falciparum CQ-sensitive strain 3D7. The quinazoline 3h was also identified as the most potent trypanosomal candidate with a selectivity index (SI) of 43 on T. brucei brucei strain. Moreover, as the telomeres of the parasites P. falciparum and Trypanosoma are possible targets of this kind of nitrogen heterocyclic compounds, we have also investigated stabilisation of the Plasmodium and Trypanosoma telomeric G-quadruplexes by our best compounds through FRET melting assays.

Keywords : antitrypanosomal activity quinoline-like derivatives Antimalarial activity G-quadruplex antileishmanial activity

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Article dans une revue

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Sciences du Vivant [q-bio] / Santé publique et épidémiologie

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Design, synthesis, and antiprotozoal evaluation of new 2,4-bis[(substituted-aminomethyl)phenyl]quinoline, 1,3-bis[(substituted-aminomethyl)phenyl]isoquinoline and 2,4-bis[(substituted-aminomethyl)phenyl]quinazoline derivatives

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Design, synthesis, and antiprotozoal evaluation of new 2,4-bis[(substituted-aminomethyl)phenyl]quinoline, 1,3-bis[(substituted-aminomethyl)phenyl]isoquinoline and 2,4-bis[(substituted-aminomethyl)phenyl]quinazoline derivatives

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