Antileishmanial activity of novel indolyl-coumarin hybrids: Design, synthesis, biological evaluation, molecular docking study and in silico ADME prediction
Antileishmanial activity of novel indolyl-coumarin hybrids: Design, synthesis, biological evaluation, molecular docking study and in silico ADME prediction
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DOI：
10.1016/j.bmcl.2015.12.085
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发表时间：
2016-02-01
影响因子：
2.7
通讯作者：
Shinde, Devanand B.
中科院分区：
文献类型：
--
作者：
Sangshetti, Jaiprakash N.;Khan, Firoz A. Kalam;Shinde, Devanand B.
本论文以Ho 3+掺杂的CoFe 2 O 4纳米粒子为催化剂，设计并合成了12个新的3-（3-（1H-吲哚-3-基）-3-苯丙酰基）-4-羟基-2H-色烯-2-酮衍生物13（a-1），并对其潜在的抗利什曼病和抗氧化活性进行了评价。发现化合物13 a、13 d和13 h具有显著的抗利什曼原虫活性（IC 50值分别为95.50、95.00和99.00 μ g/mL），与标准葡萄糖酸锑钠（IC 50 = 490.00 μ g/mL）相比。化合物13 a（IC 50 = 12.40 μ g/mL），13天（IC 50 = 13.49 μ g/mL），13g（IC 50 = 13.24 μ g/mL）和13 l（IC 50 = 13.74 μ g/mL）与标准品丁基化羟基甲苯相比，显示出良好的抗氧化活性（IC 50 = 16.5 μ g/mL）和抗坏血酸（IC 50 = 12.8 μ g/mL）。在进行分子对接研究后，发现化合物13 a和13 d具有抑制蝶啶还原酶1的潜力。计算机模拟的ADME药代动力学参数显示出有希望的结果，并且没有合成的化合物违反Lipinski的五法则。因此，表明本系列化合物可以作为设计和开发新的抗利什曼原虫和抗氧化剂的重要途径。(C)2016爱思唯尔有限公司版权所有
In present work we have designed and synthesized total twelve novel 3-(3-(1H-indol-3-yl)-3-phenylpropanoyl)-4-hydroxy-2H-chromen-2-one derivatives 13(a-l) using Ho3+ doped CoFe2O4 nanoparticles as catalyst and evaluated for their potential antileishmanial and antioxidant activities. The compounds 13a, 13d and 13h were found to possess significant antileishmanial activity (IC50 value = 95.50, 95.00 and 99.00 mu g/mL, respectively) when compared to the standard sodium stibogluconate (IC50 = 490.00 mu g/mL). The compounds 13a (IC50 = 12.40 mu g/mL), 13d (IC50 = 13.49 mu g/mL), 13g (IC50 = 13.24 mu g/mL) and 13l (IC50 = 13.74 mu g/mL) had shown good antioxidant activity when compared with standards butylated hydroxy toluene (IC50 = 16.5 mu g/mL) and ascorbic acid (IC50 = 12.8 mu g/mL). After performing molecular docking studies, it was found that compounds 13a and 13d had potential to inhibit pteridine reductase 1 enzyme. In silico ADME pharmacokinetic parameters had shown promising results and none of the synthesized compounds had violated Lipinski's rule of five. Thus, suggesting that compounds from the present series can serve as important gateway for the design and development of new antileishmanial as well as antioxidant agent. (C) 2016 Elsevier Ltd. All rights reserved.