Sadek Bassem, Limban Carmen, Stecoza Camelia Elena, Elz Sigurd
Department of Pharmacology and Therapeutics, Faculty of Medicine and Health Sciences, United Arab Emirates University, P.O. Box 17666, Al-Ain, United Arab Emirates.
Sci Pharm. 2011 Oct-Dec;79(4):749-61. doi: 10.3797/scipharm.1107-02. Epub 2011 Sep 18.
A series of dibenzo[b,e]ox(thi)epin-11(6H)-one O-benzoyloximes has been synthesized and structurally elucidated by means of IR, (1)H-NMR, (13)C-NMR, MS, and elemental analysis. The newly developed compounds were screened at concentrations of 200-25 μg/mL for their antibacterial activity against Gram+ve organisms such as Methicillin-Resistant Staphylococcus Aureus (MRSA), Gram-ve organisms such as Escherichia coli (E. coli), and at the same concentration range for their antifungal activity against fungal strain Aspergillus niger (A. niger) by the cup plate method. Ofloxacin and ketoconazole (10 μg/mL) were used as reference standards for antibacterial and antifungal activity, respectively. The dibenzo[b,e]oxepines 6a-c and 6e-h showed low antimicrobial activity (MIC 125-200 μg/mL) compared to the reference substances, whereas a major improvement (MIC 50-75 μg/mL) was achieved with the synthesis of the corresponding bromomethyl derivative 6d. Moreover, replacement of oxygen by its bioisosteric sulfur led to isomeric dibenzo[b,e]thi-epine derivatives 6g,h which significantly exhibited higher antimicrobial activity (MIC 25-50 μg/mL) against all tested culture strains used in the present study, demonstrating that a change of chemical class from dibenzo[b,e]oxepine to dibenzo[b,e]thiepine significantly improves the antimicrobial activity. Further variation, such as the oxidation of the thiepine sulfur to the corresponding isomeric dibenzo[b,e]thiepine 5,5-dioxide derivative 9, comparatively failed to exhibit high activity (MIC 200 μg/mL) against S. aureus, E. coli or A. niger.
合成了一系列二苯并[b,e]氧（硫）杂环庚因-11(6H)-酮O-苯甲酰肟，并通过红外光谱、¹H-核磁共振、¹³C-核磁共振、质谱和元素分析对其结构进行了阐明。通过杯碟法，对新合成的化合物在200 - 25μg/mL浓度下针对革兰氏阳性菌如耐甲氧西林金黄色葡萄球菌（MRSA）、革兰氏阴性菌如大肠杆菌（E. coli）进行了抗菌活性筛选，同时在相同浓度范围内针对真菌菌株黑曲霉（A. niger）进行了抗真菌活性筛选。氧氟沙星和酮康唑（10μg/mL）分别用作抗菌和抗真菌活性的参考标准。与参考物质相比，二苯并[b,e]氧杂环庚因6a - c和6e - h显示出较低的抗菌活性（最低抑菌浓度为125 - 200μg/mL），而相应的溴甲基衍生物6d的合成则实现了显著改善（最低抑菌浓度为50 - 75μg/mL）。此外，用其生物电子等排体硫取代氧得到了异构的二苯并[b,e]硫杂环庚因衍生物6g,h，它们对本研究中使用的所有测试培养菌株均表现出显著更高的抗菌活性（最低抑菌浓度为25 - 50μg/mL），这表明从二苯并[b,e]氧杂环庚因到二苯并[b,e]硫杂环庚因的化学类别变化显著提高了抗菌活性。进一步的变体，如将硫杂环庚因硫氧化为相应的异构二苯并[b,e]硫杂环庚因5,5 - 二氧化物衍生物9，相对而言对金黄色葡萄球菌、大肠杆菌或黑曲霉未表现出高活性（最低抑菌浓度为200μg/mL）。
