Hemi-synthesis of novel (S)-carvone hydrazone from Carum carvi L. essential oils: structural and crystal characterization, targeted bioassays and molecular docking on human protein kinase (CK2) and Epidermal Growth factor Kinase (EGFK)

Polyfunctional N,O,O,N-type ligands such as the oxalyl dihydrazide (ODH) may induce formation of mono- , di-, and polynuclear complexes with natural monoterpene ketones, involving ligand bridging and Oxo- bridging. In this context, a novel chiral dihydrazone is designed through hemi-synthesis process by re- acting oxalyldihydrazide (ODH) with ( s )-carvone, the major compound of caraway’s seeds essential oil. The C = N imine bi-condensation is performed without prior isolation of the natural ( s )-carvone and the resulting ( s )-carvone dihydrazone (s-CHD) is structurally characterized by Single-crystal X-ray diffrac- tion, 2D-NMR spectroscopy and chiral LCMS analysis to confirm the formation of a single pure enan- tiomer. In -vitro cell-based assays were conducted on normal fibroblast (L929) using a presBlue (PB) flu- orescence quantification method of cell-viability and by sulforhodamine B calorimetric cytotoxicity as- says to determine the anti-proliferative effect on four human tumoral lines (NCI-H460, Hela, HepG2 and MCF-7) and normal PLP2. Anti-inflammatory assays were determined through NO production by Maurine LPS-stimulated macrophages (RAW 264.7). The ( s )-CHD has no effect on normal cells viability ( > 88%) and PLP2 (GI50 = 326 ug/mL), while a moderate ( ∼55%) to significant ( ∼63%) antigrowth potential was recorded against HepG2, Hela and MCF-7 tumor cell lines, where RAW 264.7 was feebly sensitive. A molecular docking was performed using Autodock vina software on the protein kinase CK2 and Epi- dermal Growth factor Kinase proteins EGFK and the dock scores allowed to identify significant bind- ing affinities (lower G and Ki values) and potential hydrophilic/hydrophobic interactions with ( s )-CHD comparing to the clinical ellipticine as potential ligands. Molecular docking suggests that ( s )-CHD pos- sesses high affinity towards the kinase domain receptors CK2 and EGFR, being able to bind to the ATP region.Thanks are due to the Research Center Scientific and Technical in Analyzes Physico-Chimiques CRAPC Algerian Directorate for research DGRSDT for the financial support. The authors thanks Fundação para a Ciência e a Tecnologia (FC&T, Lisbon) for financial support through projects PTDC/MEC–ONC/29327/2017 and PTDC/EQU-EQU/32473/2017. We are thankful to NOVA University of Lisbon (FCT/UNL) for the financial support from Erasmus + EU international credit mobility 2017–2019. the laboratory for Green Chemistry LAQV-REQUIMTE FCT/MCTES (UID/QUI/50006/2019) is co-financed by the ERDF and the chemistry department for providing the instruments support.info:eu-repo/semantics/publishedVersio

A step-by-step synthesis of triazole-benzimidazole-chalcone hybrids: Anticancer activity in human cells+

Novel series of triazole-benzimidazole-chalcone hybrid compounds have been synthesized via click chemistry, between different azide derivatives and substituted benzimidazole terminal alkynes bearing a chalcone moiety. The starting alkynes are prepared via base-catalysed nitrogen alkylation of pre-synthetized benzimidazole-chalcone substrates. All the intermediates as well as the final products are fully characterized by 1D and 2D NMR and mass spectrometry techniques. HMBC correlations permits the identification of a unique 1,4-disubstitued triazole-benzimidazole-chalcone isomer. Evaluation of the anti-proliferative potential in breast and prostate cancer cell lines showed that the presence of chloro substituents at the chalcone ring of the triazole-benzimidazole-chalcone skeleton enhanced the cytotoxic effects. The benzyl group linked to the 1,2,3-triazole moiety provides more antiproliferative potential.publishe

Hemi-Synthesis of Chiral Imine, Benzimidazole and Benzodiazepines from Essential Oil of Ammodaucus leucotrichus subsp. leucotrichus

The hemi-synthesis of chiral imine, benzimidazole and benzodiazepine structures is reported by the condensation of (S)-(−)-perillaldehyde, the major phytochemical of Ammodaucus leucotrichus subsp. leucotrichus essential oil, with different amine derivatives of 2,3-diaminomaleonitrile, o-phenylenediamine and 3-[(2-aminoaryl)amino]dimedone. The reaction proceeds in situ at ambient temperature without prior isolation of the natural (S)-(−)-perillaldehyde. Final products precipitate in the ethanolic reaction medium. 2D NMR and single-crystal X-ray diffraction studies were used to unequivocally characterize the structures in solution and in the solid state, respectively. Chiral HPLC analysis confirms the formation of unique enantiomers and diastereomeric mixtures

Hemi-synthesis of novel (S)-carvone hydrazone from Carum carvi L. essential oils: structural and crystal characterization, targeted bioassays and molecular docking on human protein kinase (CK2) and Epidermal Growth factor Kinase (EGFK)

Polyfunctional N,O,O,N-type ligands such as the oxalyl dihydrazide (ODH) may induce formation of mono-, di-, and polynuclear complexes with natural monoterpene ketones, involving ligand bridging and Oxo-bridging. In this context, a novel chiral dihydrazone is designed through hemi-synthesis process by reacting oxalyldihydrazide (ODH) with (s)-carvone, the major compound of caraway's seeds essential oil. The C = N imine bi-condensation is performed without prior isolation of the natural (s)-carvone and the resulting (s)-carvone dihydrazone (s-CHD) is structurally characterized by Single-crystal X-ray diffraction, 2D-NMR spectroscopy and chiral LCMS analysis to confirm the formation of a single pure enantiomer. In-vitro cell-based assays were conducted on normal fibroblast (L929) using a presBlue (PB) fluorescence quantification method of cell-viability and by sulforhodamine B calorimetric cytotoxicity assays to determine the anti-proliferative effect on four human tumoral lines (NCI-H460, Hela, HepG2 and MCF-7) and normal PLP2. Anti-inflammatory assays were determined through NO production by Maurine LPS-stimulated macrophages (RAW 264.7). The (s)-CHD has no effect on normal cells viability (>88%) and PLP2 (GI50= 326 ug/mL), while a moderate (∼55%) to significant (∼63%) antigrowth potential was recorded against HepG2, Hela and MCF-7 tumor cell lines, where RAW 264.7 was feebly sensitive. A molecular docking was performed using Autodock vina software on the protein kinase CK2 and Epidermal Growth factor Kinase proteins EGFK and the dock scores allowed to identify significant binding affinities (lower ΔG and Ki values) and potential hydrophilic/hydrophobic interactions with (s)-CHD comparing to the clinical ellipticine as potential ligands. Molecular docking suggests that (s)-CHD possesses high affinity towards the kinase domain receptors CK2 and EGFR, being able to bind to the ATP region.publishe