A Newly Synthesized β-amino-α, β-unsaturated Ketone Derivative of β-himachalene: Structural, NBO, NLO, and Molecular Docking Studies

In the current study, a new β-amino-α,β-unsaturated ketone-based himachalene ((1S,3R,8R)-9-amino-2,2-dichloro-3,7,7,10-tetramethyltricyclo[6.4.0.01,3]dodec-9-en-11-one) (4) was synthesized from β-himachalene (1) extracted from essential oil of Atlas Cedar. The β-amino-α, β-unsaturated ketone product (4) was characterized by 1D NMR (1H, 13C) and 2D NMR (HSQC, COSY, NOESY), FTIR analysis, and single-crystal X-ray diffraction. The title compound, C16H23Cl2NO, crystallizes with two molecules in the asymmetric unit with similar conformations. One of the two molecules is characterized by chlorine and one-methyl position disorder. In the crystal, intermolecular N—H…O hydrogen bonds lead to forming a three-dimensional framework. In addition, the molecular structure of the title compound was examined by Hirshfeld topology analysis and Density Functional Theory (DFT) using B3LYP calculations at 6-311+G(d,p) level. The optimized structure parameters were compared with the experimental result, an excellent correlation between theoretical structures parameters and experimental values was found. The natural bond orbitals (NBO) analysis and the first-order hyperpolarizability were also performed. Moreover, two biological activities were examined for product 4 against Acetylcholinesterase and Cytochrome P450 3A4, which bind to similar fragments with molecular docking. We find good scores and binding affinity of our molecule to link to these two proteins.Cadi Ayyad UniversityChouaib Doukkali UniversityMohammed V Universit

Evaluation of Anticancer and Anti-Inflammatory Activities of Some Synthetic Rearranged Abietanes

This research was funded by grants from the Regional Government of Andalusia (Projects B-FQM-278-UGR20, and B-FQM-650-UGR-20), and assistance was provided to the group FQM-348.Supplementary Materials: The following supporting information can be downloaded at https://www.mdpi.com/article/10.3390/ijms241713583/s1Synthesis of the rearranged abietane diterpenes pygmaeocins C and D, viridoquinone, saprorthoquinone, and 1-deoxyviroxocine has been successfully achieved. The anticancer and anti-inflammatory activities of selected orthoquinonic compounds 5, 7, 13, and 19, as well as pygmaeocin C (17), were evaluated for the first time. The antitumor properties were assessed using three cancer cell lines: HT29 colon cancer cells, Hep G2 hepatocellular carcinoma cells, and B16-F10 murine melanoma cells. Compounds 5 and 13 showed the highest cytotoxicity in HT29 cells (IC50 = 6.69 ± 1.2 µg/mL and IC50 = 2.7 ± 0.8 µg/mL, respectively). Cytometric studies showed that this growth inhibition involved phase S cell cycle arrest and apoptosis induction, possibly through the activation of the intrinsic apoptotic pathway. Morphological apoptotic changes, including nuclear fragmentation and chromatin condensation, were also observed. Furthermore, the anti-inflammatory activity of these compounds was evaluated on the basis of their ability to inhibit nitric oxide production on the lipopolysaccharide activated RAW 264.7 macrophage cell line. Although all compounds showed high anti-inflammatory activity, with percentages between 40 and 100%, the highest anti-inflammatory potential was obtained by pygmaeocin B (5) (IC50NO = 33.0 ± 0.8 ng/mL). Our results suggest that due to their dual roles, this type of compound could represent a new strategy, contributing to the development of novel anticancer agents.Regional Government of Andalusia B-FQM-278-UGR20, B-FQM-650-UGR-20, FQM-34

Versatile synthesis of cadalene and iso-cadalene from himachalene mixtures: Evidence and application of unprecedented rearrangements

International audienceFrom a mixture of α-, β- and γ-himachalenes extracted from waste wood of Atlas cedar (Cedrus atlantica), cadalene (1,6-dimethyl-4-isopropylnaphthalene) and iso-cadalene (1,6-dimethyl-3-isopropylnaphthalene) were produced in two steps with up to 71% ± 5% yield through the ar-himachalene intermediate using I2 and/or AlCl3 as reagents. The selectivity is shown to sharply depend on the operating conditions: while I2/AlCl3 in dichloromethane promotes the formation of cadalene, the formation of iso-cadalene is favored in the presence of AlCl3 in cyclohexane. The bicyclic aromatic compounds were thus obtained through unique rearrangements involving sequential CC bond cleavage/formation and hydride transfer processes. In the absence of AlCl3 or I2, dihydrocurcumene was also found to be formed with up to 70% selectivity. A tentative mechanism is proposed and discussed