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

发布时间：2018-04-04 14:43

本文选题：磺胺　切入点：-三唑　出处：《有机化学》2017年12期

【摘要】：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?g/m L).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.
[Abstract]:Sulfonamides are important chemotherapeutic drugs, and the design and synthesis of new sulfonamides is one of the hot research fields in recent years.A series of new sulfonamides were synthesized from acetanilide by sulfonylation, ammonolysis and N-alkylation. The structures of these compounds were confirmed by IR ~ 1H NMR-13C NMRMS and HRMS.The antibacterial and antifungal activities of the synthesized sulfamethoxazole compounds were investigated in vitro. The results showed that the synthesized compounds were superior to sulfonamides, and the compounds generally showed good anti-Escherichia coli activities.In particular, N-N- (4-N- (2-H-) 1H-1H ~ (-1)) 2-triazole-1-yl) ethyl (N-N-(3-fluorobenzyl) sulfonyl) (phenyl) phenyl) acetamide (7b)) showed a better activity against Escherichia coli (MIC16g / m 路L ~ (-1) ~ (-1)).In addition, in order to explore the possible mechanism of antimicrobial action, the interaction between 7b, a highly active compound, and calf thymus DNA was studied by UV spectroscopy.It is suggested that compound 7b may form a complex with DNA by intercalation, thus exerting antimicrobial effect.
【作者单位】：临沂大学药学院;西南大学化学化工学院;
【基金】：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) 国家级大学生创新创业训练计划资助项目~~
【分类号】：O626.26;TQ460.1

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