Synthesis and biological evaluation of new 2-Amino-7-hydroxy-8-methyl-4-aryl-4H-chromene-3-carbonitrile derivatives

Abstract

A series of new 2-amino-7-hydroxy-8-methyl-4-aryl-4H-chromene-3-carbonitrile derivatives (4a-4g) have been synthesized by a one-pot multicomponent reaction of 2-methylresorcinol (1) and malononitrile (2) with various aldehydes (3). All the synthesised compounds (4a-4g) have been characterised using FT-IR, ¹H NMR, ¹³C NMR, HR-MS and evaluated for swarming behaviour, biofilm formation, biofilm disruption and urease activity against P. mirabilis (MTCC-425). Among all the synthesized compounds, compounds 4a, 4b and 4g showed slightly inhibited swarming behaviour and compounds 4f and 4g inhibited biofilm formation with increasing concentration. SEM (Scanning Electron Microscope) imaging shows that compound 4e effectively disrupts the preformed biofilm. Also, compounds 4d and 4e showed 40% reduction in urease activity. The SAR studies of synthesized compounds are elaborated in detail to provide key structural features. Furthermore, molecular docking studies against urease could provide a mechanistic basis for the inhibition. The per-residue interaction analysis suggested the involvement of non-bonded and bonded interactions with the active site of urease. Hence, the aim of the below study was to synthesize new chromene derivatives and study their biological activities.

GRAPHICAL ABSTRACT

Keywords:

• Multicomponent reaction
• One-pot synthesis
• 4H-chromene
• Biofilm
• Molecular docking

Supporting Information

Experimental procedure, Experimental protocol for the biological activity and molecular docking, IR, ¹H NMR, ¹³C NMR, HRMS spectra of the compounds and Molecular docking Figures (S29 to S34).