Hemi-synthesis, in-vitro and in-silico bioactivities of new chiral-Schiff bases and benzodiazepine derivatives from Ammodaucus leucotrichus(S)-perillaldehyde

Abstract

A new series of benzodiazepines and chiral Schiff bases have been prepared by an in situ condensation of (S)-(-)-perillaldehyde, occurring naturally in the essential oil of Ammodaucus leucotrichus subsp. Leucotrichus, with various amines, hydrazines, and oxalyl dihydrazide. Pure enantiomeric compounds TK1-6 have been obtained in moderate to good yields, after spontaneous precipitation in ethanol. The structures have been identified by one- and two-dimensional NMR experiments, FTIR, and single-crystal X-ray. To confirm the formation of unique Schiff base enantiomers and diastereomeric mixtures of benzodiazepines, chiral HPLC was used. All the new derivatives were screened for their antioxidant and antibacterial activities. The antioxidant activity has been evaluated using the DPPH-scavenging activity method, in which the benzodiazepines show an excellent activity compared to gallic acid. The antimicrobial studies revealed the highest inhibition of the chloro-benzodiazepine derivative against MSSA, MRSA, and M. luteus with MIC values between 0.125-0.25mg/mL when compared with metronidazole used as reference. Molecular docking performed on the penicillin-binding protein (PBP2a) from methicillin-resistant S. aureus MRSA has demonstrated sensitivity towards the novel Schiff Bases.