S-Euglobals:: Biomimetic synthesis, antileishmanial, antimalarial, and antimicrobial activities
S-Euglobals:: Biomimetic synthesis, antileishmanial, antimalarial, and antimicrobial activities
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DOI：
10.1016/j.bmc.2007.10.055
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发表时间：
2008-02-01
影响因子：
3.5
通讯作者：
Singh, Inder Pal
中科院分区：
文献类型：
--
作者：
Bharate, Sandip B.;Khan, Shabana I.;Singh, Inder Pal
以间苯三酚为原料，通过Knoevenagel缩合和单萜[4+2]-Diels-Alder环加成的仿生三组分反应，合成了几种新的正global类似物（称为s-正global）。新合成的真全球类似物包含天然真全球中尚未遇到的单萜烯。S-Euglobals与先前合成的robustadial A和B的体外抗利什曼原虫、抗疟疾、抗菌和细胞毒活性进行了评估。在16种类似物中，发现9种类似物对多诺瓦利什曼原虫具有抗利什曼原虫活性。类似物7最有效，IC50为2.4 μ g/mL， IC90为8 μ g/mL，其次是类似物8和11 （IC50为5.5和9.5 μ g/mL）。鲁棒菌A(5)和B(6)的抗虫活性中等，IC50分别为20和16 μ g/mL。罗布斯塔丁A、B和s - global 8对恶性疟原虫的抗疟活性较弱（IC50为2.7 ~ 4.76 μ g/mL）。对耐甲氧西林金黄色葡萄球菌表现出抑菌活性。其中，类似物I I最有效，IC50为1.0 μ g/mL， MIC为5.0 μ g/mL。大多数化合物在由癌症（SK-MEL， KB， BT-549和SK-OV-3）和非癌症肾（Vero和LLC-PK11）细胞组成的细胞系组中没有细胞毒性高达25 μ g/mL。(C) 2007 Elsevier Ltd.版权所有。
Several new euglobal analogues (named as S-euglobals) were synthesized from phloroglucinol via a biomimetic three-component reaction involving Knoevenagel condensation followed by [4+2]-Diels-Alder cycloaddition with monoterpene. Newly synthesized euglobal analogues involve monoterpenes that have not yet been encountered in natural euglobals. S-Euglobals along with previously synthesized robustadial A and B were evaluated for in vitro antileishmanial, antimalarial, antimicrobial, and cytotoxic activities. Out of 16, nine analogues were found to exhibit antileishmanial activity against Leishmania donovani promastigotes. Analogue 7 was the most potent with IC50 of 2.4 mu g/mL and IC90 of 8 mu g/mL, followed by analogues 8 and 11 (IC50 5.5 and 9.5 mu g/mL). Antilelshmanial activity of robustadial A (5) and B (6) was moderate with IC50 of 20 and 16 mu g/mL, respectively. Robustadial A and B and S-euglobal 8 exhibited weak antimalarial activity against Plasmodium falciparum (IC50 of 2.7-4.76 mu g/mL). Few of the eualobal analogues showed antibacterial activity against methicillin-resistant Staphylococcus aureus. Amongst these, analogue I I was the most potent with IC50 of 1.0 mu g/mL and MIC of 5.0 mu g/mL. Most of the compounds were not cytotoxic up to 25 mu g/mL in a panel of cell lines consisting of both cancer (SK-MEL, KB, BT-549, and SK-OV-3) as well as non-cancer kidney (Vero and LLC-PK11) cells. (C) 2007 Elsevier Ltd. All rights reserved.