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首页> 外文期刊>European Journal of Medicinal Chemistry: Chimie Therapeutique >Design, synthesis and docking studies of new furobenzopyranones and pyranobenzopyranones as photoreagent towards DNA and as antimicrobial agents.
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Design, synthesis and docking studies of new furobenzopyranones and pyranobenzopyranones as photoreagent towards DNA and as antimicrobial agents.

机译：新型呋喃啉酮和嘧苯甲酮作为光敏术朝向DNA和抗微生物剂的设计，合成和对接研究。

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A number of new furobenzopyranones and pyranobenzopyranones carrying an electron-withdrawing function at the position 3 are synthesized in order to obtain new photoreagents towards DNA. Our interest in this study is to investigate the effect of introduction of electron withdrawing function on the position 3 of the benzo-a-pyranone ring of linear furobenzo-a-pyranone (5,8-dimethoxypsoralen) or angular pyranobenzo-a-pyranone on the biological activity, by preparing 3-cyano, carboxylic acid, carboxylic acid ester, acid hydrazide, thiosemicarbazide, or mercaptotriazole derivatives. 5-acetyl-6-hydroxybenzofuran, and 8-acetyl-7-hydroxy-4-phenylbenzopyranone are the key starting compounds on which 3-cyano-4-methylfurobenzopyranone and 3-cyano-4-methyl pyranobenzopyranone moieties were built respectively. The photobiological activity of the newly synthesized compounds was evaluated. It looks most promising for enhancement of photoreactivity of compounds towards DNA, and a certain effect was observed in the dark determining the antimicrobial activity. Compounds 5, 6, 7, 13, 14 exhibit potential photoreactivity towards DNA, while 3-mercaptotriazole derivatives 7, 14 possess only photosensitizing activity. To investigate the antimicrobial data on structural basis, molecular modelling and docking studies of the tested compounds into the crystal structure of topoisomerase II DNA Gyrase B complexed with the natural inhibitor bearing the coumarin moiety clorobiocin (1kzn), using Molsoft ICM 3.4-8C program was performed in order to predict the affinity and orientation of the synthesized compounds at the active site. The ICM score values and hydrogen bonds formed with the surrounding amino acids show good agreement with predicted binding affinities obtained by molecular docking studies as verified by antimicrobial screening, where compounds 5, 6, 13 were the most active compounds against Bacillus subtilis, Staphylococcus aureus, and Escherichia coli. Compound 13 has good affinity with the receptor and forms six hydrogen bonds with Asp-73, and two bonds with Thr-165, compound 6 has ICM score value -85.66 and forms one hydrogen bond with Asp-73, and three with Thr-165, and compound 5 has ICM score value -53 but forms one hydrogen bond with Asp-73, and four bonds with Thr-165 which may reveal the potent antimicrobial activity referred to the natural antimicrobial Clorobiocin which forms two hydrogen bonds with Asp-73 and three with Thr-165.
机译：合成了许多新的呋喃啉甲苯和致吡喃吡喃酮和致吡喃吡喃酮，其在位置3处携带电子提取功能，以获得朝向DNA的新型光致作用。我们对本研究的兴趣是探讨引入电子提取功能在直线呋喃酮（5,8-二甲氧基索伦）或角嘧啶虫酮的苯并-α-吡喃酮环的位置3上的效果通过制备3-氰基，羧酸，羧酸酯，酸酰肼，硫代氧化脲或巯基三唑衍生物来制备生物活性。 5-乙酰-6-羟基苯脲和8-乙酰基-7-羟基-4-苯基苯并吡喃酮是其中构建了3-氰基-4-甲基吡咯烷酮和3-氰基-4-甲基吡喃酮部分的关键起始化合物。评价新合成化合物的光生物活性。它看起来最有希望为增强化合物朝向DNA的光反应性，并且在黑暗测定抗微生物活性中观察到某种效果。化合物5,6,7,13,14表现出朝向DNA的电位光反应性，而3-巯基唑衍生物7,14只具有光敏活性。为了研究关于结构基础的结构基础的抗微生物数据，使用Molsoft ICM 3.4-8C计划将测试化合物与含有香豆素部分Clorociocin（1KZN）的天然抑制剂复合的TOPOISOMERASE II DNA旋转酶B晶体结构的分子建模和对接研究。进行以预测活性位点在合成化合物的亲和力和取向。与周围氨基酸形成的ICM评分值和氢键显示出通过通过抗微生物筛查的分子对接研究获得的预测结合亲和力，其中化合物5,6,13是对枯草芽孢杆菌，金黄色葡萄球菌的最活性化合物，和大肠杆菌。化合物13与受体具有良好的亲和力，并与ASP-73形成六个氢键，两种与Thr-165的键，化合物6具有ICM评分值-85.66，并与ASP-73形成一个氢键，三个用THR-165形成一个氢键。和化合物5具有ICM得分值-53，但与ASP-73形成一种氢键，与三键与THR-165形成，其可以揭示用ASP-73形成两个氢键的天然抗微生物克罗飞酶的有效抗微生物活性。三个用thr-165。

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