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

• Published in: Journal of molecular structure 2021-10, Vol.1241, p.130690, Article 130690
• Main Authors: Khalfaoui, Massaab, Chebrouk, Farid, Ziani, Borhane E.C., Bennamane, Norah, Cherfaoui, Brahim, Frites, Wahiba, Valega, Mónica, Mendes, Ricardo F., Paz, Filipe A. Almeida, Chebout, Redouan, Bachari, Khaldoun, Talhi, Oualid, Silva, Artur M.S.
• Format: Article
• Language: English
• Subjects: (S)-(-)-perillaldehyde; Amines; Ammodaucus leucotrichus; Biological activity; Chiral-HPLC; Essential oil; Hemi-synthesis; Molecular docking; NMR; Single-crystal X-ray diffraction
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2021.130690

•Benzodiazepines and chiral Schiff bases were hemi-synthetized from the natural (S)-(-)-perillaldehyde of A. leucotrichus.•Structures were chemically characterized by NMR, FTIR and X-Ray crystallin analysis.•Enantio-pure Schiff bases and diastereomeric mixtures of benzodiazepines were confirmed by chiral- HPLC analysis.•Benzodiazepines exhibit better antioxidant activity, while Schiff base derivatives were effective against bacterial strains.•Molecular docking suggested penicillin-binding protein of MRS. aureus as a possible target of Schiff Bases. 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. [Display omitted]