Synthesis, Biological Screening and Docking Study of Some Novel Pyrazolopyrano[ 2,3-B]quinolin Derivatives as Potent Antibacterial Agents

Abstract

Background: Pyranopyrazoles have a variety of biological activities and can be obtained by various starting materials and synthetic methods. Also, pyrazolopyrano[2,3-b]quinolins that contain pyranopyrazole moiety have some biological activities such as anti-acetylcholinesterase and anti-butyrylcholinesterase activity. In this research, our objective is to prepare pyranopyrazole compounds and pyrazolopyrano[2,3-b]quinolins in a simple way and then evaluate their antibacterial effect. Methods: In this study, pyrano[2,3-c]pyrazole derivatives have been synthesized by condensing malononitrile, aromatic aldehydes, and 3-methyl-1-phenyl-2-pyrazolin-5-one in the presence of magnesium perchlorate as a catalyst. Then we prepared pyrazolopyrano[2,3-b]quinolins via subsequent Friedlander reaction between cyclohexanone and the obtained pyrano[2,3-c]pyrazoles. Also, the antimicrobial activity of the synthesized pyrazolopyrano[2,3-b]quinolins against Staphylococcus aureus, Methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli was measured. Then we studied molecular docking of them to find the predicted compounds' interactions and binding energy with DNA-gyrase with the AutoDock 4.2 software. Results: Pyrazolopyrano[2,3-b]quinolins were synthesized in the optimized conditions. Evaluation of their antibacterial activities showed that these compounds have moderate to good antibacterial activities against four bacteria species. Also molecular docking tests of docked compounds showed a strong bonding interaction with DNA-Gyrase and had been docked into the intercalation place of DNA of DNA-gyrase complex. The molecule bonded to the DNA stabilized by the H bonds, hydrophobic interactions, and π-π interaction. Conclusion: We have developed an efficient and one-pot ecofriendly protocol for the synthesis of some novel pyrano[2,3-c]pyrazol derivatives and pyrazolopyrano[2,3-b]quinolins under simple conditions and then tested them for their antibacterial activities. Also, we studied molecular docking of them. These compounds showed moderate to good inhibitory action.