含氧、氮、硫杂环化合物的合成、生物活性及分子对接研究

IF 2.2 4区 化学 Q3 CHEMISTRY, MULTIDISCIPLINARY
Abdel Haleem M. Hussein, Abu-Bakr A. El-Adasy, Ahmed M. El-Saghier, Aboubakr H. Abdelmonsef, M. Olish
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引用次数: 0

摘要

本研究设计并合成了一系列新的含氧、氮和硫的杂环化合物。因此,3-氧丁酰胺1与丙二腈和氰乙酸乙酯缩合得到吡啶酮衍生物4a;4 b。1与丙二腈和硫元素反应生成噻吩衍生物8和与芳基化合物9a &;9b, 15产生了建议的结构11a &;11b和18。此外,1与对氨基酚和/或水合肼缩合分别得到22和23。另外,用2-氨基三唑修饰的三唑嘧啶27处理1。1与所制备的偶氮化合物29重氮化偶联得到熔融吡唑酮衍生物31。最后,1与查尔酮反应生成吡啶酮衍生物36。所有合成化合物的结构通过不同的光谱技术(IR, 1H-, 13C-NMR和MS)得到证实。此外,对合成的化合物进行了体外抑菌活性筛选,检测其对革兰氏阳性菌(包括casseliflavus、kristinae、溶血链球菌和枯草芽孢杆菌)以及革兰氏阴性菌(包括大肠杆菌)的抑菌活性。化合物27和36对所有菌株均表现出较强的抑菌活性。此外,对合成的化合物对大肠杆菌FabH-CoA复合物结构(PDB ID: 1hnj)进行分子对接研究,确定其结合作用模式。硅实验结果与生物学实验结果一致,化合物27和36对靶蛋白的结合亲和度分别为- 9.3和- 9.0 kcal/mol。综上所述,化合物27和36可用于开发抗菌抑制剂。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Synthesis, biological activity and molecular docking study of some new compounds incorporating oxygen-, nitrogen-, and sulfur- heterocycles

Synthesis, biological activity and molecular docking study of some new compounds incorporating oxygen-, nitrogen-, and sulfur- heterocycles

In the present study, a new series of oxygen-, nitrogen-, and sulfur- heterocycles linked to benzyl moiety was designed and synthesized. So, condensation of 3-oxobutanamide 1 with malononitrile and ethyl cyanoacetate afforded the pyridinone derivative 4a & 4b. Reaction of 1 with malononitrile and sulfur element yielded thiophene derivative 8 and with arylidines 9a & 9b, 15 yielded the proposed structures 11a & 11b and 18. Further, condensation of 1 with p-aminophenol and/or hydrazine hydrate gave 22 and 23, respectively. Also, treatment of 1 with 2-amino triazole furnished triazole pyrimidinone 27. Diazotization and coupling of 1 with prepared azo compound 29 afforded the fused pyrazolone derivative 31. Finally, reaction of 1 with chalcone furnished the pyridinone derivative 36. The elucidation of structures of all synthesized compounds was confirmed by means of different spectroscopic techniques (IR, 1H-, 13C-NMR, and MS). In addition, the synthesized compounds were screened for their in vitro antibacterial activities against Gram-positive bacteria, including E. casseliflavus, K. kristinae, S. haemolyticus and B. subtilis, along with Gram-negative bacteria, including E. coli. Compound 27, followed by 36 exhibited highly antibacterial activities against all bacterial strains. Moreover, molecular docking studies were performed for the synthesized compounds against E. coli FabH-CoA complex structure (PDB ID: 1hnj) to identify their binding mode of actions. The results of in silico studies are in agreement with the biological studies, as compounds 27 and 36 showed the best binding affinities (− 9.3 and − 9.0 kcal/mol) against the target, respectively. In conclusion, compounds 27 and 36 could be utilized for development antibacterial inhibitors.

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来源期刊
CiteScore
4.40
自引率
8.30%
发文量
230
审稿时长
5.6 months
期刊介绍: JICS is an international journal covering general fields of chemistry. JICS welcomes high quality original papers in English dealing with experimental, theoretical and applied research related to all branches of chemistry. These include the fields of analytical, inorganic, organic and physical chemistry as well as the chemical biology area. Review articles discussing specific areas of chemistry of current chemical or biological importance are also published. JICS ensures visibility of your research results to a worldwide audience in science. You are kindly invited to submit your manuscript to the Editor-in-Chief or Regional Editor. All contributions in the form of original papers or short communications will be peer reviewed and published free of charge after acceptance.
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