Faculty of Chemistry, University of Warsaw, Pasteura 1, 02-093 Warszawa, Poland.
Chair and Department of Biochemistry, Medical University of Warsaw, 02-097 Warszawa, Poland.
Int J Mol Sci. 2021 Dec 29;23(1):378. doi: 10.3390/ijms23010378.
Eleven novel imide-tetrazoles were synthesized. In the initial stage of research, in silico structure-based pharmacological prediction was conducted. All compounds were screened for antimicrobial activity using standard and clinical strains. Within the studied group, compounds - were recognized as leading structures with the most promising results in antimicrobial studies. Minimal inhibitory concentration values for compounds , , were within the range of 0.8-3.2 μg/mL for standard and clinical Gram-positive and Gram-negative bacterial strains, showing in some cases higher activity than the reference Ciprofloxacin. Additionally, all three inhibited the growth of all clinical panels: (T5592; T5591) and (5253; 4243) with MIC values of 0.8 μg/mL. Selected compounds were examined in topoisomerase IV decatenation assay and DNA gyrase supercoiling assay, followed by suitable molecular docking studies to explore the possible binding modes. In summary, the presented transition from substrate imide-thioureas to imide-tetrazole derivatives resulted in significant increase of antimicrobial properties. The compounds - proposed here provide a promising basis for further exploration towards novel antimicrobial drug candidates.
合成了 11 种新型酰亚胺-四唑化合物。在研究的初始阶段，进行了基于结构的计算机药理学预测。使用标准和临床菌株筛选所有化合物的抗菌活性。在所研究的组中，化合物 - 被认为是具有最有前途的抗菌研究结果的主导结构。化合物 、 、 的最小抑菌浓度值在 0.8-3.2 μg/mL 范围内，适用于标准和临床革兰氏阳性和革兰氏阴性细菌菌株，在某些情况下比参考药物环丙沙星具有更高的活性。此外，所有三种化合物均抑制所有临床 组的生长：(T5592; T5591)和 (5253; 4243)，MIC 值为 0.8 μg/mL。选择的化合物在拓扑异构酶 IV 解链试验和 DNA 回旋酶超螺旋化试验中进行了检查，随后进行了适当的分子对接研究，以探索可能的结合模式。总之，从底物酰亚胺-硫脲到酰亚胺-四唑衍生物的转变导致抗菌性能显著提高。本文提出的化合物 - 为进一步探索新型抗菌药物候选物提供了有希望的基础。
