Facile Synthesis of 6-Phenyl-6h-chromeno [4, 3-b] Quinoline Derivatives using NaHSO4@SiO2 Re-usable Catalyst and Their Antibacterial Activity Study Correlated by Molecular Docking Studies

Abstract

Background: Heterocyclic compounds containing heteroatoms (O, N and S) as part of five or six-membered cyclic moieties exhibited various potential applications, such as pharmaceutical drugs, agrochemical products and organic materials. Among many known heterocyclic moieties, quinoline and its derivatives are one of the privileged scaffolds found in many natural products. In general, quinoline derivatives could be prepared by utilizing ortho-substituted anilines and carbonyl compounds containing a reactive α-methylene group of well-known reaction routes like Friedlander synthesis, Niemantowski synthesis and Pfitzinger synthesis. Moreover, polysubstituted quinolones and their derivatives also had shown considerable interest in the fields of organic and pharmaceutical chemistry in recent years. Objective: The main objective of our research work is towards the design and synthesis of divergent biological-oriented, proactive analogues with potential pharmacological value inspired by the anti-tubercular activity of 2-phenylquinoline analogues. In this study, we have been interested in the design and synthesis of bioactive, 2, 4-diphenyl, 8-arylated quinoline analogues. Methods: 6-phenyl-6h-chromeno [4, 3-b] quinoline derivatives were synthesized from 4-chloro-2- phenyl-2H-chromene-3-carbaldehyde and various substituted aromatic anilines as starting materials using sodium bisulfate embedded SiO2 re-usable catalyst. All these fifteen new compound structures confirmed by spectral data 1H & 13C NMR, Mass, CHN analysis etc. Furthermore, all these new compounds antibacterial activity strains recorded using the paper disc method. The compound molecular structures were designed using molecular docking study by utilizing the crystallographic parameters of S. Areus Murb protein. Results: A series of fifteen new quinoline derivatives synthesized in moderate to good yields using sodium bisulfate embedded SiO2 re-usable catalyst. The molecular structures of these newly synthesized compounds elucidated by the combination of spectral data along with the elemental analysis. These compounds antibacterial activity study have shown moderate to good activity against, Escherichia coli (Gram-negative) and Staphylococcus aureus (gram-positive) organisms. These antibacterial activity results were also a very good correlation with molecular docking studies. Conclusion: In this study, fifteen new quinoline derivatives synthesized and structures confirmed by spectral data. In fact, all the compounds have shown moderate to good antibacterial activity. In general, the compounds containing the electron donor group at R1 position (R1 = OMe) and the acceptor group at R2 positions (R2 = F or Cl) had shown good antibacterial activity. These antibacterial activity results were also a very good correlation with molecular docking studies showing strong binding energies with the highest value being, -12.45 Kcal mol-1 with S. aureus MurB receptor.