Thanh Tung Truong, Xuan Huy Luong, Quoc Thang Nguyen
PHENIKAA University Hanoi 12116 Vietnam
PHENIKAA Institute for Advanced Study (PIAS), PHENIKAA University Hanoi 12116 Vietnam.
RSC Adv. 2021 Aug 26;11(46):28797-28808. doi: 10.1039/d1ra03616e. eCollection 2021 Aug 23.
Quorum sensing is a well-known term for describing bacterial cell-cell communication. Bacteria use quorum sensing pathways to respond to external factors such as nutrient availability, defense mechanisms, and coordinate host toxic behaviors such as biofilm formation, virulence production, and other pathogenesis. Discovery of novel compounds which inhibit quorum sensing without being antibiotic are currently emerging fields. Herein, the library of fifteen benzo[]thiazole/quinoline-2-thiol bearing 2-oxo-2-substituted-phenylethan-1-yl compounds was designed, synthesized and evaluated to find novel quorum sensing inhibitors. Firstly, compounds were evaluated for their growth inhibitory activities at high concentrations up to 1000 μg mL toward . Under our conditions, twelve compounds showed moderate growth inhibitory activities in the concentration tested. To our delight, three compounds 3, 6 and 7 do not affect the growth of the bacteria which were chosen for the evaluation of quorum sensing inhibitor activities. In the system, our compounds 3, 6, 7 showed promising quorum-sensing inhibitors with IC of 115.2 μg mL, 182.2 μg mL and 45.5 μg mL, respectively. In the system, no activity observed suggesting that the selectivity of the compound toward the system. In addition, 7 showed the moderate anti-biofilm formation of . Docking studies revealed that 3, 6 and 7 binding to the active site of quorum sensing system with better affinity compared to reference compounds 4-NPO. Finally, computation calculations suggest that compounds are a good template for further drug development.
群体感应是描述细菌细胞间通讯的一个广为人知的术语。细菌利用群体感应途径来响应外部因素，如营养可用性、防御机制，并协调宿主毒性行为，如生物膜形成、毒力产生和其他发病机制。发现能够抑制群体感应而不具有抗生素作用的新型化合物是当前正在兴起的研究领域。在此，设计、合成并评估了包含十五种带有2-氧代-2-取代苯基乙-1-基的苯并噻唑/喹啉-2-硫醇的化合物库，以寻找新型群体感应抑制剂。首先，评估了这些化合物在高达1000 μg/mL的高浓度下对……的生长抑制活性。在我们的实验条件下，十二种化合物在测试浓度下表现出中等程度的生长抑制活性。令我们高兴的是，三种化合物3、6和7对被选用于评估群体感应抑制剂活性的细菌的生长没有影响。在……系统中，我们的化合物3、6、7显示出有前景的群体感应抑制剂活性，其IC值分别为115.2 μg/mL、182.2 μg/mL和45.5 μg/mL。在……系统中，未观察到活性，这表明该化合物对……系统具有选择性。此外，7显示出对……的中等程度的抗生物膜形成作用。对接研究表明，与参考化合物4-NPO相比，3、6和7以更好的亲和力结合到……群体感应系统的活性位点。最后，计算结果表明这些化合物是进一步药物开发的良好模板。
