0 avis
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
Archive ouverte
Edité par CCSD -
International audience. 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 thesenovel aza derivatives was evaluated on human HepG2 cells. The phenanthroline 1f was noticed as the most potent antimalarialcandidate 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 mostactive compounds with an IC50 of 2.08 mM. In addition, the phenanthrolines 1f and 1i were also identified as the most promisingtrypanosomal candidates with selectivity index (SI) of 231.1 and 143.7, respectively on T. brucei brucei strain. As the telomeres ofthe parasites P. falciparum and Trypanosoma could be considered as possible targets of this kind of aza heterocyclic molecules, theirability to stabilize the parasitic telomeric G-quadruplexes have been measured through the FRET melting assay.
Consulter en ligne
Suggestions
Du même auteur
