Synthesis, Antimicrobial Capability and Molecular Docking of Heterocyclic Scaffolds Clubbed by 2-Azetidinone, Thiazole and Quinoline Derivatives

Abstract

A new set of molecules was designed and synthesized by compilation of pharmacologically potential segments thiazole and quinoline bridged by 2-azetidinone as a linker in a single molecular skeleton. Structural analysis of synthesized molecules (5a-p) was executed by IR, ¹H NMR, ¹³C NMR, and mass spectroscopy techniques. Aforesaid compounds were analyzed for investigation of their antimicrobial capability against several bacterial and fungal strains. The synthesized compounds 5b, 5f, 5h, 5i, 5k, and 5l were active against bacterial strains while compounds 5j and 5k were active against fungal strains. Synthesized compounds were found to be potential inhibitors against gram-negative bacterial strains Escherichia coli and Pseudomonas aeruginosa, while the same were not effective against gram-positive strains of Staphylococcus aureus and Streptococcus pyogenes. Compounds with electron-releasing substituents were active molecules against all fungal strains used in screening. Also, the influence of substituents on the antimicrobial activity of target molecules (5a-p) was discussed. Molecular docking study against crucial microbial target β-Ketoacyl-acyl carrier protein (ACP) synthase III (FabH) could provide valuable insights into their plausible mechanism of action.

Keywords:

• 2-azetidinone
• antimicrobial capability
• molecular docking
• quinoline
• thiazole

Acknowledgments

One of the authors Prof. Nisheeth C Desai is thankful to the University Grant Commission, New Delhi for awarding BSR Faculty-Fellowship 2019 (No. F 18-1/2011 (BSR)) and financial assistance. Miss Jahnvi D. Monapara is grateful to Department of Science and Technology, Government of India, INSPIRE FELLOWSHIP PROGRAM [No. IF180817]. Authors are thankful to the University Grants Commission, New Delhi and Department of Science and Technology, New Delhi for financial support under the NON-SAP and DST-FIST programs respectively. Authors also thank Schrödinger Inc. for providing Small-Molecule Drug Discovery Suite to perform the molecular docking studies. Authors are also thankful to Priyanka Desai, founder of iScribblers for the English editing portion of the manuscript.

Disclosure statement

The authors declare that they have no conflict of interest.