Abstract
Background: Recently, the essential oil (EO) of Ammodaucus leucotrichus has attracted particular attention in hemi-synthesis due to the reactivity of its main monoterpenes.
Objective: In vitro cytotoxic and antileishmanial activities of the EO and hemi-synthesized compounds were evaluated, and an in-silico simulation was conducted.
Methods: The EO was characterized by GC-MS. Two benzodiazepines (C1, C2), benzimidazole (C3), and Schiff base (C4) were hemi-synthesized by an in situ condensation of its major monoterpenes (perillaldehyde) with different amine derivatives. Synthesized compounds and the EO were evaluated for their cytotoxic activity against laryngeal carcinoma-Hep2 and rhabdomyosarcoma-RD cell lines and for their antileishmanial activity against Leishmania (L) major. Molecular docking was performed to pin the binding interactions of active molecules.
Results: A significant cytotoxic effect of benzodiazepines C1 and C2 was noted against Hep2 cells (IC50/C1 = 39.48 ±0.7 μM, IC50/C2 = 48.82±1.33 μM) and RD (IC50/C1 = 15.96±1.99 μM; IC50/C2 = 74.3±2.44 μM), while the EO highly inhibited Hep2 cell lines (IC50/EO = 17.3±0.85 μg/mL). C4 strongly inhibited L. major growth with an IC50 value of 8.00±1.37 Μμ. The docking scores of ligand-C4 on L. major pteridine reductase and L. major methionyl-tRNA synthetase and ligands-(C1, C2) on the human protein kinase and epidermal growth factor kinase presented significant affinity to the receptor active sites (ΔG from -7.7 to -8.8 kcal/mol).
Conclusion: The cytotoxic effect of derivatives C1, C2, and EO, as well as the anti-parasitic effect of C4, may suggest them as effective bioactive agents or pharmaceutical probes.
Keywords: Perilalldehyde, Ammodaucus leucotrichus, hemi-synthesis, essential oil, biological activity, molecular docking.
Graphical Abstract
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