Synthesis, Biological and Molecular Docking Studies of New Polysubstituted 2‐Amino‐3‐Cyano‐4H‐Chromene Derivatives

Abstract

A series of new substituted 2‐amino‐3‐cyano‐4H‐chromene derivatives have been synthesised by one pot multicomponent reaction of substituted benzaldehyde, malononitrile and 4‐chloro resorcinol. All the synthesised compounds have been characterised using FT‐IR, 1H NMR, 13C NMR and HR‐MS spectra and screened for bioactivities such as swarming behaviour, biofilm formation, biofilm disruption, urease production in Proteus mirabilis. Whereas swarming inhibition was shown by all synthesized chromene derivatives, biofilm inhibition was shown only by nitrophenyl and fluorophenyl substituted chromene derivatives. Interestingly, urease activity was shown by meta substituted nitrophenyl and fluorophenyl derivatives. Quantitative polymerase chain (qPCR) reaction used to investigate the molecular mechanism of most active chromene derivatives showed prominent down regulations of urease enzyme genes. Molecular docking study against urease supported the observed bioactive effect and provide valuable insights into the binding modes and affinities of these new chromene derivatives. The per‐residue interaction analysis proposed the involvement of non‐bonded (steric and electrostatic) and bonded (hydrogen bonding and pi‐pi stacking) interactions with the active site.