In order to develop novel antimicrobial agents, we prepared quinoline bearing pyrimidine analogues 2-7, 8a-d and 9a-d and their structures were elucidated by spectroscopic techniques. Furthermore, our second aim was to predict the interactions between the active compounds and enzymes (DNA gyrase and DHFR). In this work, fourteen pyrimido[4,5-b]quinoline derivatives were prepared and assessed for their antimicrobial potential by estimating zone of inhibition. All the screened candidates displayed antibacterial potential with zone of inhibition range of 9-24 mm compared with ampicillin (20-25 mm) as a reference drug. Moreover, the target derivatives 2 (ZI = 16), 9c (ZI = 17 mm) and 9d (ZI = 16 mm) recorded higher antifungal activity against C. albicans to that exhibited by the antifungal drug amphotericin B (ZI = 15 mm). Finally, the most potent pyrimidoquinoline compounds (2, 3, 8c, 8d, 9c and 9d) were docked inside DHFR and DNA gyrase active sites and they recorded excellent fitting within the active regions of DNA gyrase and DHFR. These outcomes revealed us that compounds (2, 3, 8c, 8d, 9c and 9d) could be lead compounds to discover novel antibacterial candidates.

中文翻译：

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新型嘧啶并[4,5-b]喹啉类抗菌药物的构建与对接研究

为了开发新型抗菌剂，我们制备了带有喹啉的嘧啶类似物2-7、8a-d和9a-d，并通过光谱技术阐明了它们的结构。此外，我们的第二个目标是预测活性化合物和酶（DNA 旋转酶和 DHFR）之间的相互作用。在这项工作中，制备了十四种嘧啶并[4,5-b]喹啉衍生物，并通过估计抑菌圈来评估其抗菌潜力。与作为参考药物的氨苄西林（20-25 mm）相比，所有筛选的候选药物都显示出抗菌潜力，抑制范围为 9-24 mm。此外，目标衍生物 2 (ZI = 16)、9c (ZI = 17 mm) 和 9d (ZI = 16 mm) 对白色念珠菌的抗真菌活性高于抗真菌药物两性霉素 B (ZI = 15 mm) 。最后，最有效的嘧啶并喹啉化合物（2、3、8c、8d、9c 和 9d）对接在 DHFR 和 DNA 旋转酶活性位点内，并且它们在 DNA 旋转酶和 DHFR 活性区域内记录了良好的拟合。这些结果告诉我们，化合物（2、3、8c、8d、9c 和 9d）可能是发现新型抗菌候选药物的先导化合物。