Expeditious synthesis, antileishmanial and antioxidant activities of novel 3-substituted-4-hydroxycoumarin derivatives

A series of novel 3-substituted-4-hydroxycoumarin derivatives 6(a-1) were synthesized in high yield using one-pot three component coupling reaction catalyzed by ceric ammonium nitrate. These compounds were evaluated for antileishmanial activity against Leishmania donovani promastigotes and antioxidant activity (DPPH-radical scavenging activity). Two compounds, 6h (IC50 = 9.90 mu mol/L) and 6i (IC50 = 6.90 mu mol/L) displayed potent antileishmanial activity when compared with standard antileishmanial agents pentamidine (IC50 =16.15 mu mol/L) and miltefosine (IC50 = 12.50 mu mol/L). Three compounds, 6c (IC50 = 10.79 mu,mol/L),6h(IC50 =10.60 mu mol/L), and 6i (IC50 = 10.73 mu mol/L) showed significant antioxidant activity favorably with the antioxidant standards butylated hydroxy toluene (IC50 = 16.471.1 mu mol/L) and ascorbic acid (IC50 = 12.69 mu mol/L). A molecular docking study of compounds 6(a -I) suggested a possible mode of binding with the Adenine phosphoribosyltransferase enzyme of L. donovani. ADME properties were predicted in silico and support the potential of 6(a-1) to show favorable drug-like properties. (C)2015 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. Published by Elsevier B.V. All rights reserved.