In the fight with the antimicrobial resistance, our continuous effort to find quinone analogs with higher inhibitory activity has previously led us to the promising Plastoquinone analogs. The 1,4-quinone moiety substituted with alkoxy substituent(s) plays an important role in the field of antimicrobial and anticancer drug discovery and development. Thus, an extensive series of 1,4-quinones, substituted in different positions with a variety of alkoxy substituents, has been designed, synthesized, and evaluated for their antimicrobial activity. Here, we describe the synthesis of brominated Plastoquinone analogs (BrPQ1-15) based on the dimethyl-1,4-quinone scaffold by employing two different paths. We also present here the in vitro antimicrobial activity of these analogs (BrPQ1-15) against a panel of pathogenic organisms. These studies resulted in several new selective antibacterial inhibitors and gave valuable insights into the structure-activity relationships. Among all the analogs studied, two analogs BrPQ1 with a methoxy substituent and BrPQ14 with a cyclic dioxy stand out as the most promising antibacterial molecules against Staphylococcus aureus and Staphylococcus epidermidis. Afterwards, two analogs were selected for a further investigation for biofilm evaluation. Finally, molecular docking studies for BrPQ1 and BrPQ14 with probable target S. aureus PNPase (5XEX) and predictive ADMET studies were also carried out.

在与抗菌素耐药性的斗争中，我们不断努力寻找具有更高抑制活性的醌类似物，这使我们获得了有前途的质体醌类似物。被烷氧基取代的 1,4-醌部分在抗微生物和抗癌药物的发现和开发领域发挥着重要作用。因此，已经设计、合成并评估了在不同位置被各种烷氧基取代基取代的广泛系列的 1,4-醌类化合物的抗菌活性。在这里，我们描述了基于二甲基-1,4-醌支架的溴化质体醌类似物 ( BrPQ1-15 )的合成，采用两种不同的途径。我们还在此展示了这些类似物的体外抗菌活性（BrPQ1-15 ) 对抗一组病原生物。这些研究产生了几种新的选择性抗菌抑制剂，并为结构-活性关系提供了宝贵的见解。在研究的所有类似物中，具有甲氧基取代基的两种类似物BrPQ1和具有环状二氧基的BrPQ14是最有希望的抗金黄色葡萄球菌和表皮葡萄球菌的抗菌分子。之后，选择了两种类似物进行生物膜评估的进一步研究。最后，BrPQ1和BrPQ14与可能的目标金黄色葡萄球菌的分子对接研究 还进行了 PNPase (5XEX) 和预测性 ADMET 研究。