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

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• 作者：Zahid Zaheer^a ; ^{zahidzresearch@gmail.com" class="auth_mail" title="E-mail the corresponding author} ; Firoz A. Kalam Khan^a ; Jaiprakash N. Sangshetti^a ; Rajendra H. Patil^b
• 关键词：4-Hydroxycoumarin ; Ceric ammonium nitrate ; Antileishmanial activity ; Antioxidant activity ; Molecular docking study ; ADME properties
• 刊名：Chinese Chemical Letters
• 出版年：2016
• 出版时间：February 2016
• 年：2016
• 卷：27
• 期：2
• 页码：287-294
• 全文大小：1042 K

文摘

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.