Aarjane Mohammed, Slassi Siham, Tazi Bouchra, Amine Amina
Laboratory of Chemistry/Biology Applied to the Environment, University Moulay Ismail, Meknes, Morocco.
Department of Basic Sciences, National School of Agriculture, Meknes, Morocco.
Arch Pharm (Weinheim). 2020 Dec 2:e2000261. doi: 10.1002/ardp.202000261.
The present study was carried out in an attempt to synthesize a new class of potential antibacterial agents. In this context, novel isoxazoles were synthesized and evaluated for their potential antibacterial behavior against four pathogenic bacterial strains. The synthesized compounds exhibited moderate-to-good antibacterial activity against these strains. The highest antibacterial activity was observed against the Escherichia coli strains, particularly for compounds 4a and 4e with phenyl and para-nitrophenyl groups on the isoxazole-acridone skeleton; they showed promising minimum inhibitory concentration values of 16.88 and 19.01 μg/ml, respectively, compared with the standard drug chloramphenicol (22.41 µg/ml). The synthesized compounds were subjected to in silico docking studies to understand the mode of their interactions with the DNA topoisomerase complex (PDB ID: 3FV5) of E. coli. The molecular docking results showed that compounds 4a-l occupy the active site of DNA topoisomerase (PDB ID: 3FV5), stabilized via hydrogen bonding and hydrophobic interactions, which may be the reason behind their interesting in vitro antibacterial activity.
本研究旨在合成一类新型潜在抗菌剂。在此背景下，合成了新型异恶唑并评估了它们对四种致病细菌菌株的潜在抗菌性能。合成的化合物对这些菌株表现出中度至良好的抗菌活性。对大肠杆菌菌株观察到最高的抗菌活性，特别是异恶唑 - 吖啶酮骨架上带有苯基和对硝基苯基的化合物4a和4e；与标准药物氯霉素（22.41μg/ml）相比，它们分别显示出有前景的最低抑菌浓度值16.88和19.01μg/ml。对合成的化合物进行了计算机对接研究，以了解它们与大肠杆菌DNA拓扑异构酶复合物（PDB ID：3FV5）相互作用的模式。分子对接结果表明，化合物4a - l占据DNA拓扑异构酶（PDB ID：3FV5）的活性位点，通过氢键和疏水相互作用稳定，这可能是它们有趣的体外抗菌活性背后的原因。
