Synthesis and Antimalarial Evaluation of New 1,3,5-<i>tris</i>[(4-(Substituted-aminomethyl)phenyl)methyl]benzene Derivatives: A Novel Alternative Antiparasitic Scaffold

• Main Authors: Sandra Albenque-Rubio (Author), Jean Guillon (Author), Anita Cohen (Author), Patrice Agnamey (Author), Solène Savrimoutou (Author), Stéphane Moreau (Author), Jean-Louis Mergny (Author), Luisa Ronga (Author), Ioannis Kanavos (Author), Serge Moukha (Author), Pascale Dozolme (Author), Pascal Sonnet (Author)
• Format: Book
• Published: MDPI AG, 2023-08-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

A series of new 1,3,5-<i>tris</i>[(4-(substituted-aminomethyl)phenyl)methyl]benzene compounds were designed, synthesized, and evaluated <i>in vitro</i> against two parasites (<i>Plasmodium falciparum</i> and <i>Leishmania donovani</i>). The biological results showed antimalarial activity with IC₅₀ values in the sub and μM range. The <i>in vitro</i> cytotoxicity of these new aza polyaromatic derivatives was also evaluated on human HepG2 cells. The 1,3,5-<i>tris</i>[(4-(substituted-aminomethyl)phenyl)methyl]benzene <b>1m</b> was found as one of the most potent and promising antimalarial candidates with a ratio of cytotoxic to antiprotozoal activities of 83.67 against the <i>P. falciparum</i> CQ-sensitive strain 3D7. In addition, derivative <b>1r</b> was also identified as the most interesting antimalarial compound with a selectivity index (SI) of 17.28 on the W2 <i>P. falciparum</i> CQ-resistant strain. It was previously described that the telomeres of <i>P. falciparum</i> could be considered as potential targets of these kinds of aza heterocycles; thus, the ability of these new derivatives to stabilize the parasitic telomeric G-quadruplexes was measured through a FRET melting assay.

Item Description

10.3390/ddc2030033
2813-2998