Synthesis, antibacterial, anti-oxidant and molecular docking studies of imidazoquinolines

K Velmurugan; Derin Don; Rajesh Kannan; C Selvaraj; S VishnuPriya; G Selvaraj; S K Singh; R Nandhakumar

doi:10.1016/j.heliyon.2021.e07484

Synthesis, antibacterial, anti-oxidant and molecular docking studies of imidazoquinolines

Heliyon. 2021 Jul 5;7(7):e07484. doi: 10.1016/j.heliyon.2021.e07484. eCollection 2021 Jul.

Authors

K Velmurugan¹, Derin Don¹, Rajesh Kannan², C Selvaraj³, S VishnuPriya⁴, G Selvaraj⁵, S K Singh³, R Nandhakumar¹

Affiliations

¹ Department of Applied Chemistry, Karunya Institute of Technology and Sciences (Deemed-to-be University), Karunya Nagar, Coimbatore, 641 114, India.
² Department of Microbiology, Bharathidasan Univeristy, Tiruchirappalli, 620 024, India.
³ Computer Aided Drug Design and Molecular Modeling Lab, Department of Bioinformatics, Science Block, Alagappa University, Karaikudi, 630004, Tamil Nadu, India.
⁴ Department of Medical Neurobiology, Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem, 91120, Israel.
⁵ Centre for Interdisciplinary Sciences-Computational Life Sciences, College of Food Science and Technology, Henan University of Technology, Zhengzhou, China.

Abstract

Quinoline and imidazole derivatives have been playing a significant role in functional bioactivities and were potentially used as antibacterial, antifungal, anticancer, and anti-inflammatory drugs. Owing to the limitation of drug resistance, herein we synthesized thio-, chloro-, and hydroxyl-functionalized various imidazoquinolines by molecular hybridization approach. All the imidazoquinoline derivatives were examined for their antibacterial activity against selected bacterial pathogens by the agar well diffusion method. In addition, the anti-oxidant efficacy of imidazoquinolines was also tested using ferric reducing antioxidant power (FRAP). Among them, electron-withdrawing (-Cl) substituent containing imidazoquinoline 5f showed higher antibacterial and anti-oxidant activities than other imidazoquinolines and reached the effectiveness of the standard. In addition, compounds 4f, 5e, and 3f showed moderate antibacterial activity and other derivatives displayed weak activity against various pathogens. Molecular docking studies were also performed on selected imidazoquinoline derivatives (3f, 4f, and 5f), which showed high docking score and strong binding energy values. These results revealed that thio-imidazoquinoline could assist as a prototype for the designing of multidrug-resistant antibiotics against various microbial organisms.

Keywords: 2-Chloro-3-formylquinolines; Antibacterial; Antioxidant; Chloro-imidazoquinolines; Hydroxy-imidazoquinolines; Molecular docking; Multidrug-resistant; Thio-imidazoquinolines.