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...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 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-1） 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.展开更多
文摘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 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-1） 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.
