Synthesis, spectroscopic characterization, antimicrobial evaluation and molecular docking study of novel triazine-quinazolinone based hybrids
Synthesis, spectroscopic characterization, antimicrobial evaluation and molecular docking study of novel triazine-quinazolinone based hybrids
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DOI：
10.1016/j.molstruc.2017.11.087
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发表时间：
2018-03-15
影响因子：
3.8
通讯作者：
Asadi, Parvin
中科院分区：
文献类型：
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作者：
Dinari, Mohammad;Gharahi, Fateme;Asadi, Parvin
报道了一系列新型含喹唑啉酮结构的1，3，5-三嗪类抗菌剂。三聚氯氰（1）的第一个氯基团被苯胺取代，第二个被各种芳香胺取代。使所制备的一氯三嗪与肼反应，随后使其与2-甲基-4H-苯并[1，3]恶嗪-4-酮反应，以获得新的基于三嗪-喹唑啉酮的杂化物（9a-f）。通过薄层色谱、熔点、傅里叶变换红外光谱（FTIR）、H-1和C-13 NMR谱和元素分析等技术对杂化化合物的化学结构和纯度进行了评价。采用连续肉汤稀释法对3种革兰氏阴性菌（沙门氏菌、大肠杆菌、铜绿假单胞菌）、3种革兰氏阳性菌（金黄色葡萄球菌、李斯特菌、枯草芽孢杆菌）以及酵母样真菌白色念珠菌进行了抗菌活性研究。其中，具有苯磺酰胺基团的化合物9d显示出较高的抗微生物活性，其最小抑制浓度（MIC）值为16 μ g/mL。此外，化合物5d、9a和9 b对几种测试菌株显示出良好的活性。此外，还进行了对接模拟，将最佳抗菌化合物定位到S。金黄色葡萄球菌二氢叶酸还原酶（DHFR）活性位点，以确定可能的结合构象。(C)2017爱思唯尔B. V.保留所有权利。
A new series of 1,3,5-triazine incorporating aromatic quinazolinone moieties as a potential antimicrobial agents is reported. The first chlorine group of the cyanuric chloride (1) was replaced by aniline and the second one was replaced by various aromatic amines. The prepared monochlorotriazine was allowed to react with hydrazine and subsequently it was reacted with 2-methyl-4H-benzo[1,3]oxazin-4-one to obtain novel triazine-quinazolinone based hybrids (9a-f). The chemical structure and purity of the hybrid compounds were evaluated by different techniques such as thin layer chromatography, melting point, Fourier-transform infrared (FTIR), H-1 and C-13 NMR spectra and elemental analysis. Antimicrobial activity of the hybrid compounds were study by three Gram-negative bacteria (Salmonella entritidis, Escherichia coli, Pseudomonas aeruginosa) and three Gram-positive bacteria (Staphylococcus aureus, Listeria monocitogenes, Bacillus subtilis) as well as Candida albicansas a yeast-like fungus using the serial broth dilution method. Among them, compound 9d with benzenesulfonamide group showed higher antimicrobial activity with a minimum inhibitory concentration (MIC) value of 16 mu g/mL. Furthermore, compounds 5d, 9a and 9b showed good activity against several tested strains. In addition, docking simulation was perform to position best antibacterial compounds in to the S. aureus dihydrofolate reductase (DHFR) active site to determine the probable binding conformations. (C) 2017 Elsevier B.V. All rights reserved.