新型磺胺1,2,4-三唑类化合物的设计合成、抗微生物活性及与小牛胸腺DNA相互作用研究
收稿日期: 2017-08-06
修回日期: 2017-09-02
网络出版日期: 2017-09-19
基金资助
国家自然科学基金（No.21672173）、山东省自然科学基金（No.ZR2017PB001，ZR2016CP22）、临沂大学博士启动基金（No.LYDX2016BS030）和国家级大学生创新创业训练计划资助项目.
Design, Synthesis, and Biological Evaluation of Novel Sulfonamide 1,2,4-Triazoles and Their Interaction with Calf Thymus DNA
Received date: 2017-08-06
Revised date: 2017-09-02
Online published: 2017-09-19
Supported by
Project supported by the National Natural Science Foundation of China (No. 21672173), the Shandong Provincial Natural Science Foundation (No. ZR2017PB001, ZR2016CP22), the Doctoral Scientific Research Foundation of Linyi University (No. LYDX2016BS030) and the National Innovative Training Program for College Students.
磺胺类药物是重要的化学治疗药物，设计合成新型的磺胺类药物是近年来研究的热点领域之一.以乙酰苯胺为起始原料，经过磺酰化、氨解、N-烷化等多步反应合成了一系列新型磺胺1，2，4-三唑类化合物，其结构经IR、1H NMR、13C NMR、MS和HRMS证实.体外考察了合成的磺胺三唑类化合物的抗细菌和抗真菌活性，结果表明所合成化合物的活性优于磺胺，且化合物普遍给出较好的抗大肠杆菌活性，特别是N-（4-（N-（2-（1H-1，2，4-三唑-1-基）乙基）-N-（3-氟苄基）磺酰氨基）苯基）乙酰胺（7b）显示较优的抗大肠杆菌活性（MIC=16 μmg/mL）.此外，为了初步探讨化合物可能的抗微生物作用机制，利用紫外光谱法初步研究了强活性化合物7b与小牛胸腺DNA的相互作用.研究表明化合物7b可能通过嵌入的方式与DNA形成复合物进而发挥抗微生物效力.
刘庆龙 , 房鹏金 , 赵志龙 , 张慧珍 , 周成合 . 新型磺胺1,2,4-三唑类化合物的设计合成、抗微生物活性及与小牛胸腺DNA相互作用研究[J]. 有机化学, 2017 , 37(12) : 3146 -3154 . DOI: 10.6023/cjoc201708010
Sulfonamides as an important type of chemotherapeutic drugs have been one of the research topics recently. A series of sulfonamide 1,2,4-triazoles were successfully synthesized starting from commercial acetanilide via a multi-step sequence of sulfonylation, aminolysis and N-alkylation, and were confirmed by IR, 1H NMR, 13C NMR, MS as well as HRMS spectra. All the synthesized new compounds were evaluated for their in vitro antibacterial and antifungal activities. The bioactive assay showed that most of the synthesized compounds exhibited better inhibitory potency than sulfanilamide against all tested bacterial strains, and most of the compounds gave good anti-Escherichia coli activity in comparison with other microorganisms. Especially, N-(4-(N-(2-(1H-1,2,4-triazol-1-yl)ethyl)-N-(3-fluorobenzyl)sulfamoyl)phenyl) acetamide (7b) bearing m-fluorobenzyl group exhibited excellent antibacterial activities against Escherichia coli with minimal inhibition concentration (MIC) value of 16 mg/mL. Preliminary research revealed that compound 7b could effectively intercalate into calf thymus DNA to form compound 7b-DNA complex which might block DNA replication and thus exert antimicrobial activities.
Key words： sulfonamide; 1,2,4-triazole; synthesis; antimicrobial; calf thymus DNA
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