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

• Päätekijät: Sandra Albenque-Rubio (Tekijä), Jean Guillon (Tekijä), Anita Cohen (Tekijä), Patrice Agnamey (Tekijä), Solène Savrimoutou (Tekijä), Stéphane Moreau (Tekijä), Jean-Louis Mergny (Tekijä), Luisa Ronga (Tekijä), Ioannis Kanavos (Tekijä), Serge Moukha (Tekijä), Pascale Dozolme (Tekijä), Pascal Sonnet (Tekijä)
• Aineistotyyppi: Kirja
• Julkaistu: MDPI AG, 2023-08-01T00:00:00Z.
• Aiheet: article
• Linkit: Connect to this object online.
• Notes: 10.3390/ddc2030033; 2813-2998
• Keywords: antimalarial activity; 1,3,5-<i>tris</i>[(4-(substituted-aminomethyl)phenyl)methyl]benzene; antileishmanial activity; Pharmacy and materia medica; RS1-441; Chemistry; QD1-999
• Source: Drugs and Drug Candidates, Vol 2, Iss 3, Pp 653-672 (2023)

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.