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

A series of novel 3-substituted-4-hydroxycoumarin derivatives 6(a–l) 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 μmol/L) and 6i (IC50 = 6.90 μmol/L) displayed potent antileishmanial activity when compared with standard antileishmanial agents pentamidine (IC50 = 16.15 μmol/L) and miltefosine (IC50 = 12.50 μmol/L). Three compounds, 6c (IC50 = 10.79 μmol/L), 6h (IC50 = 10.60 μmol/L), and 6i (IC50 = 10.73 μmol/L) showed significant antioxidant activity favorably with the antioxidant standards butylated hydroxy toluene (IC50 = 16.47 μmol/L) and ascorbic acid (IC50 = 12.69 μmol/L). A molecular docking study of compounds 6(a–l) 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–l) to show favorable drug-like properties.

A series of novel 3-substituted-4-hydroxycoumarin derivatives 6(a–l) were synthesized in high yield using one-pot three component coupling reaction catalyzed by ceric ammonium nitrate. The synthesized compounds had displayed promising antileishmanial and antioxidant activities.Figure optionsDownload as PowerPoint slide