Construction and Docking Studies of Novel Pyrimido[4,5‐b]quinolines as Antimicrobial Agents

Abstract

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.