四唑化合物开环反应、晶体结构及相关抗微生物作用研究

目的 为了解决日益严重的耐药性问题，合成得到了四唑开环化合物3。方法 5-氨基四唑1和4-乙酰氨基苯磺酰氯2在碳酸钾存在下反应得到四唑开环化合物3，并采用倍比稀释法和棋盘法测试了化合物的抗微生物活性及与临床药物的联用效果，最后使用紫外-可见光谱法测试了化合物与小牛胸腺DNA的相互作用。结果 X-射线单晶衍射证实5-氨基四唑断键开环生成叠氮化物3含有一个结晶水分子，属于P-1空间群，晶胞参数a = 7.5554(5) Å，b = 8.8163(4) Å，c = 11.0516(7) Å，a = 75.463(5) °，b = 89.813(5) °，g = 69.166(6) °。化合物通过氧原子、氮原子和氢原子形成氢键，进而形成三维超分子结构。化合物的抗细菌和抗真菌活性，结果表明所合成化合物的对所测试的细菌和真菌显示了较弱到中等(MIC = 64~256 mg·mL^-1)的抑制活性。化合物与临床药物联用后，明显增强了抗微生物能力，显示较好的协同作用效果。化合物3与小牛胸腺DNA相互作用的紫外吸收光谱显示，化合物可能通过嵌入DNA形成复合物，从而发挥抗微生物作用。结论 化合物3可作为潜在的临床抗微生物候选药物。

The ring-opening reaction of tetrazole compound, crystal structure and relevant bioactivity exploration

Objective To incidence of resistance, the tetrazole ring-opening compound 3 was synthesized and evaluated.Methods The reaction of 5-amino tetrazole 1 with 4-acetamidobenzene-1-sulfonyl chloride 2 in the presence of potassium carbonate afforded the ring-opening compound 3. The antimicrobial activity and combination studies with clinical drugs of the prepared compounds were screened bytwo-fold serial dilution technique and microdilution checkerboard method. The UV-Vis absorption spectroscopy was employed to study the interaction of compound 3 with calf thymus DNA.Results X-ray single diffraction showed that 3 bearing one lattice water molecule belongs to space group P-1 with the following cell parameters: a = 7.5554(5) Å, b = 8.8163(4) Å, c = 11.0516(7) Å, a = 75.463(5) °, b = 89.813(5) °, g = 69.166(6) °.Furthermore,these 1D-chains are assembled into a three-dimensional supramolecular structure via hydrogen bonds among oxygen, nitrogen and hydrogen atoms.The bioactive assay showed that they exhibited weak to moderate activity against the tested strains with MIC values ranging from 64 to 256 mg·mL^-1. In addition, the combination of compound 3 with reference drugs displayed stronger antimicrobial efficiency and better synergistic effects.The UV-Vis absorption spectroscopy of the specific interaction of compound 3 with calf thymus DNA demonstrated that compound 3 might intercalate into calf thymus DNA to form compound 3-DNA complex, and thus exert antimicrobial activities.Conclusion Compound 3 could serve as potential clinical antimicrobial candidate.