Sluga Janja, Tomašič Tihomir, Anderluh Marko, Rambaher Martina Hrast, Bajc Gregor, Sevšek Alen, Martin Nathaniel I, Pieters Roland J, Novič Marjana, Venko Katja
Laboratory for Cheminformatics, Theory Department, National Institute of Chemistry, Hajdrihova ulica 19, 1000 Ljubljana, Slovenia.
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Ljubljana, Aškerčeva cesta 7, 1000 Ljubljana, Slovenia.
Antibiotics (Basel). 2024 Aug 10;13(8):751. doi: 10.3390/antibiotics13080751.
Bacteria are capable of remarkable adaptations to their environment, including undesirable bacterial resistance to antibacterial agents. One of the most serious cases is an infection caused by multidrug-resistant , which has unfortunately also spread outside hospitals. Therefore, the development of new effective antibacterial agents is extremely important to solve the increasing problem of bacterial resistance. The bacteriolytic enzyme autolysin E (AtlE) is a promising new drug target as it plays a key role in the degradation of peptidoglycan in the bacterial cell wall. Consequently, disruption of function can have an immense impact on bacterial growth and survival. An in silico and in vitro evaluation of iminosugar derivatives as potent inhibitors of (AtlE) was performed. Three promising hit compounds (, and ) were identified as AtlE binders in the micromolar range as measured by surface plasmon resonance. The most potent compound among the SPR response curve hits was , with a of 19 μM. The value for compound was 88 μM, while compound had a value of 410 μM.
细菌能够对其环境进行显著的适应性变化，包括产生不良的细菌对抗菌剂的耐药性。最严重的情况之一是由多重耐药菌引起的感染，不幸的是，这种感染也已经传播到医院之外。因此，开发新的有效抗菌剂对于解决日益严重的细菌耐药性问题极为重要。溶菌酶自溶素E（AtlE）是一个有前景的新药物靶点，因为它在细菌细胞壁肽聚糖的降解中起关键作用。因此，其功能的破坏会对细菌的生长和存活产生巨大影响。对亚氨基糖衍生物作为自溶素E（AtlE）的有效抑制剂进行了计算机模拟和体外评估。通过表面等离子体共振测定，鉴定出三种有前景的命中化合物（、和）为微摩尔范围内的AtlE结合剂。SPR响应曲线命中的化合物中最有效的是，其解离常数为19μM。化合物的解离常数为88μM，而化合物的解离常数为410μM。
