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


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 TK16 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. (c) 2021 Elsevier B.V. All rights reserved.



subject category

Chemistry, Physical


Khalfaoui, M; Chebrouk, F; Ziani, BEC; Bennamane, N; Cherfaoui, B; Frites, W; Valega, M; Mendes, RF; Paz, FAA; Chebout, R; Bachari, K; Talhi, O; Silva, AMS

our authors


We would like to thank the General Directorate for Scientific Research and Technological Development -DGRSDT of Algeria for financing the research. Thanks are due to University of Aveiro and FCT/MEC for the financial support to the QOPNA research group, financed by national funds and when appropriate co-financed by FEDER under the PT2020 Partnership Agreement, and to the Portuguese NMR Network. This work was developed within the scope of the project CICECO-Aveiro Institute of Materials, UIDB/50 011/2020 & UIDP/50011/2020, financed by national funds through the FCT/MEC and when appropriate co-financed by FEDER under the; PT2020 Partnership Agreement. FCT is also gratefully acknowledged for the Junior Research Position CEECIND/00553/2017 (to RFM).

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