Aurones: a promising heterocyclic scaffold for the development of potent antileishmanial agents.
A series of (Z)-2-benzylidenebenzofuran-3-(2H)-ones (aurones) bearing a variety of substituents on rings A and B were synthesized and evaluated for their antiparasitic activity against the intracellular amastigote form of Leishmania infantum and their cytotoxicity against human THP1-differentiated macrophages. In general, aurones bearing no substituents on ring A (compounds 4a-4f) exhibit higher toxicity than aurones with 4,6-dimethoxy substitution (compounds 4g-4l). Among the latter, two aurones possessing a 2'-methoxy or a 2'-methyl group (compounds 4i and 4j) exhibit potent antileishmanial activity (IC50 = 1.3 ± 0.1 μM and IC50 = 1.6 ± 0.2 μM, resp.), comparable to the activity of the reference drug Amphotericin B, whereas they present significantly lower cytotoxicity than Amphotericin B as deduced by the higher selectivity index.
Laboratory of Organic Chemistry, School of Chemical Engineering, National Technical University of Athens, Heroon Polytechniou 9, Zografou Campus, 15780 Athens, Greece.
Marina
M
Roussaki
Parasite Disease Group, IBMC-Institute for Molecular and Cell Biology, University of Porto, Rua do Campo Alegre, 823, 4150-180 Porto, Portugal.
Sofia
S
Costa Lima
Laboratory of Organic Chemistry, School of Chemical Engineering, National Technical University of Athens, Heroon Polytechniou 9, Zografou Campus, 15780 Athens, Greece.
Anna-Maria
AM
Kypreou
Department of Food Quality and Chemistry of Natural Products, Mediterranean Agronomic Institute of Chania, International Centre for Advanced Mediterranean Agronomic Studies, 73100 Chania, Crete, Greece.
Panagiotis
P
Kefalas
Parasite Disease Group, IBMC-Institute for Molecular and Cell Biology, University of Porto, Rua do Campo Alegre, 823, 4150-180 Porto, Portugal ; Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreiera, 228, 4050-313 Porto, Portugal.
Anabela
A
Cordeiro da Silva
Laboratory of Organic Chemistry, School of Chemical Engineering, National Technical University of Athens, Heroon Polytechniou 9, Zografou Campus, 15780 Athens, Greece.
Anastasia
A
Detsi