Synthesis, spectral characterization and conformational assignment of N-formyl-2,7-diaryl-1,4-diazepan-5-ones as potent antibacterial agents and type I DHQase inhibitors

Abstract

• Four N -formyldiazepan-5-ones are synthesized and characterized by IR, mass and NMR spectra. • The conformational assignment is made by NMR spectral studies. • All the formamides prefer to adopt flattened boat conformations. • Antibacterial efficacy for 9-12 have been evaluated by resazurin reduction assay. • Molecular docking is performed for 9-12 with type 1 3-DHQase protein target. Four new N -formyl-1,4-diazepan-5-ones 9-12 have been synthesized and their spectral characterization is made using IR, mass and NMR spectra. In NMR spectra, the compounds 9-12 show doubling of NMR spectral signals due to the delocalization of nitrogen lone pair into the carbonyl П cloud and thereby creating a partial double character at N C(= O ) bond which results in an equilibrium between syn and anti rotamers. The preferred conformations of N -formyl-1,4-diazepan-5-ones 9-12 are arrived from the NMR spectral data, dihedral angles (°) and destabilizing strain factors. The syn and anti rotamers of these compounds prefer to adopt equilibrium between flattened boat conformations with quasi-axial orientations of aryl groups at C-2 and C-7. Furthermore, all the compounds are active against all the tested bacterial strains. The compounds 9 & 10 against E. coli strain, compound 11 against B. cereus strain and compounds 11 & 12 against S. typhi strain show equal potency as that of standard drug Streptomycin. Hence, the formamides 9-12 are believed to be good antibacterial agents. The synthesised molecules are subjected to molecular docking studies with 3-dehydroquinate dehydratase (DHQase) protein. The molecular modelling studies exhibit high inhibition and binding energy are conforming to antibacterial activity. The compounds 9-12 exhibit better docking score and glide energy than that of DHQase co-crystallized ligand.