新型磺酰胺衍生三唑的设计与合成及生物活性探索。
Design and Synthesis of Novel Sulfonamide-Derived Triazoles and Bioactivity Exploration.
机构信息
School of Pharmacy, Linyi University, Linyi 276000, China.
School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, China.
出版信息
Med Chem. 2020;16(1):104-118. doi: 10.2174/1573406414666181106124852.
OBJECTIVE
Due to the incidence of resistance, a series of sulfonamide-derived 1,2,4- triazoles were synthesized and evaluated.
METHOD
The novel sulfonamide-derived 1,2,4-triazoles were prepared starting from commercial acetaniline and chlorosulfonic acid by sulfonylation, aminolysis, N-alkylation and so on. The antimicrobial activity of the synthesized compounds were evaluated in vitro by two-fold serial dilution technique.
RESULTS
In vitro antimicrobial evaluation found that 2-chlorobenzyl sulfonamide 1,2,4-triazole 7c exhibited excellent antibacterial activities against MRSA, B. subtilis, B. typhi and E. coli with MIC values of 0.02-0.16 μmol/mL, which were comparable or even better than Chloromycin. The preliminary mechanism suggested that compound 7c could effectively bind with DNA, and also it could bind with human microsomal heme through hydrogen bonds in molecular docking. Computational chemical studies were performed on compound 7c to understand the structural features that are essential for activity. Additionally, compound 7c could generate a small amount of reactive oxygen species (ROS).
CONCLUSION
Compound 7c could serve as a potential clinical antimicrobial candidate.
目的
由于耐药性的发生，我们合成并评价了一系列源于磺胺的 1,2,4-三唑类化合物。
方法
新型磺胺衍生的 1,2,4-三唑类化合物由商业乙酰胺和氯磺酸通过磺酰化、氨解、N-烷基化等反应合成。通过二倍稀释法评估了合成化合物的体外抗菌活性。
结果
体外抗菌评价发现，2-氯苄基磺胺 1,2,4-三唑 7c 对 MRSA、枯草芽孢杆菌、伤寒沙门氏菌和大肠杆菌具有优异的抗菌活性，MIC 值为 0.02-0.16 μmol/mL，与氯霉素相当甚至更好。初步机制表明，化合物 7c 可以与 DNA 有效结合，并且可以通过分子对接中的氢键与人体微粒体血红素结合。对化合物 7c 进行了计算化学研究，以了解对活性至关重要的结构特征。此外，化合物 7c 可以产生少量的活性氧（ROS）。
结论
化合物 7c 可以作为一种有潜力的临床抗菌候选药物。
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