Sanabria-Ríos David J, García-Del-Valle Rene, Bosh-Fonseca Sachel, González-Pagán Joangely, Díaz-Rosa Alanis, Acevedo-Rosario Karina, Reyes-Vicente Luzmarie, Colom Antonio, Carballeira Néstor M
Faculty of Science and Technology, Inter American University of Puerto Rico, Metropolitan Campus, P.O. Box 191293, San Juan, Puerto Rico 00919, United States.
Medicinal Research and Applications Laboratory, Inter American University of Puerto Rico, Metropolitan Campus, P.O. Box 191293, San Juan, Puerto Rico 00919, United States.
ACS Omega. 2024 Jul 22;9(30):32536-32546. doi: 10.1021/acsomega.4c01121. eCollection 2024 Jul 30.
is commonly found in soil and freshwater within tropical and subtropical regions. Although not a common occurrence, this bacterium has the potential to cause severe diseases in humans and animals, such as liver and lung abscesses and septicemia. Herein we report the synthesis of novel -acyl homoserine lactones (HSLs) to evaluate their effectiveness as antiquorum sensing (anti-QS) agents in . The HSLs were prepared through three synthetic approaches, where hexanoic acid, decanoic acid, 6-decynoic acid, or 2-hexadecynoic acid (2-HDA) was treated with commercially available l-homoserine lactone (HSL) hydrobromide in either dichloromethane or tetrahydrofuran in the presence of EDC and DMAP. The effectiveness of HSLs as anti-QS agents was assessed through susceptibility tests and violacein quantification. The most effective anti-QS inhibitor among all -acyl-HSLs tested was the -(2-hexadecynoyl)-l-homoserine lactone (HSL ). Further experimental approaches, such as quantification of acyl-homoserine lactones and biofilm inhibitory tests, were carried out to determine the effect of HSL on these QS-dependent mechanisms. These experiments showed that HSL was highly effective at inhibiting the production of HSLs and biofilm in at 0.25, 0.50, and 1 mg/mL. In addition, the cytotoxicity activity was evaluated against Vero cells to determine the selectivity of HSL as a nontraditional antibacterial agent. HSL was not toxic against Vero cells at concentrations ranging from 0.0039 to 1 mg/mL. Molecular docking experiments were conducted to study the interactions between novel HSLs and CviR (PDB ID 3QP5), a receptor that plays a significant role in QS. studies indicate that HSL exhibits better interactions with Leu 72 and Gln 95 of the CviR binding pocket when compared to the other analogs. These results validate previous studies, such as susceptibility tests and violacein production assays. The findings above indicate that novel acetylenic HSLs may potentially be agents that combat bacterial communication and biofilm formation. However, further investigation is necessary to expand the spectrum of bacterial strains capable of resisting antibiotics through QS and evaluate the compounds' cytotoxicity in other cell lines.
常见于热带和亚热带地区的土壤及淡水中。虽然并不常见，但这种细菌有可能在人类和动物身上引发严重疾病，如肝脓肿、肺脓肿和败血症。在此，我们报告新型酰基高丝氨酸内酯（HSLs）的合成，以评估其作为抗群体感应（anti-QS）剂在[具体对象未提及]中的有效性。HSLs通过三种合成方法制备，其中己酸、癸酸、6-癸炔酸或2-十六碳炔酸（2-HDA）在1-乙基-3-(3-二甲基氨基丙基)碳二亚胺（EDC）和4-二甲氨基吡啶（DMAP）存在下，于二氯甲烷或四氢呋喃中与市售的L-高丝氨酸内酯（HSL）氢溴酸盐反应。通过药敏试验和紫色杆菌素定量评估HSLs作为抗QS剂的有效性。在所有测试的酰基-HSLs中，最有效的抗QS抑制剂是(2-十六碳炔酰基)-L-高丝氨酸内酯（HSL）。开展了进一步的实验方法，如酰基高丝氨酸内酯的定量和生物膜抑制试验，以确定HSL对这些群体感应依赖机制的影响效果。这些实验表明，HSL在0.25、0.50和1mg/mL浓度下对[具体对象未提及]中HSLs的产生和生物膜具有高效抑制作用。此外，评估了对非洲绿猴肾细胞（Vero细胞）的细胞毒性活性，以确定HSL作为非传统抗菌剂的选择性。HSL在0.0039至1mg/mL浓度范围内对Vero细胞无毒。进行了分子对接实验，以研究新型HSLs与CviR（蛋白质数据银行ID 3QP5）之间相互作用，CviR是在[具体对象未提及]群体感应中起重要作用的一种受体。[具体研究未明确]表明，与其他类似物相比，HSL与CviR结合口袋中的亮氨酸（Leu）72和谷氨酰胺（Gln）95表现出更好的相互作用。这些结果验证了之前的[具体研究未明确]，如药敏试验和紫色杆菌素产生测定。上述研究结果表明，新型炔属HSLs可能潜在地成为对抗细菌通讯和生物膜形成的药剂。然而，有必要进一步研究，以扩大能够通过群体感应抵抗抗生素的细菌菌株范围，并评估这些化合物在其他细胞系中的细胞毒性。
