Semicarbazone, thiosemicarbazone tailed isoxazoline-pyrazole: synthesis, DFT, biological and computational assessment.

Autor: Bimoussa A; Laboratory of Molecular Chemistry, unit of Organic Synthesis & Molecular Physicochemistry, Department of Chemistry, Faculty of Sciences Semlalia, PO Box 2390, Marrakech, 40001, Morocco., Hachim ME; Laboratory of Analytical & Molecular Chemistry, Polydisciplinary Faculty, Cadi Ayyad University, BP 4162, Safi, 46000, Morocco., Khatabi KE; Molecular Chemistry & Natural Substances Laboratory, Faculty of Science, University Moulay Ismail, Meknes, Morocco., Laamari Y; Laboratory of Molecular Chemistry, unit of Organic Synthesis & Molecular Physicochemistry, Department of Chemistry, Faculty of Sciences Semlalia, PO Box 2390, Marrakech, 40001, Morocco., Oubella A; Laboratory of Organic & Physical Chemistry, Faculty of Sciences, Ibnou Zohr University, Agadir, Morocco., AlAjmi MF; Department of Pharmacognosy College of Pharmacy King Saud University, Riyadh, Saudi Arabia., Auhmani A; Laboratory of Molecular Chemistry, unit of Organic Synthesis & Molecular Physicochemistry, Department of Chemistry, Faculty of Sciences Semlalia, PO Box 2390, Marrakech, 40001, Morocco., Ajana MA; Molecular Chemistry & Natural Substances Laboratory, Faculty of Science, University Moulay Ismail, Meknes, Morocco., Morjani H; BioSpectroscopie Translationnelle, BioSpecT-EA7506, UFR de Pharmacie, Université de Reims Champagne-Ardenne, 51 Rue Cognacq Jay, Reims Cedex, 51096, France., Ait Itto MY; Laboratory of Molecular Chemistry, unit of Organic Synthesis & Molecular Physicochemistry, Department of Chemistry, Faculty of Sciences Semlalia, PO Box 2390, Marrakech, 40001, Morocco.
Jazyk: angličtina
Zdroj: Future medicinal chemistry [Future Med Chem] 2024; Vol. 16 (20), pp. 2073-2086. Date of Electronic Publication: 2024 Sep 18.
DOI: 10.1080/17568919.2024.2394011
Abstrakt: Aim: A series of semicarbazone and thiosemicarbazone-tailed hybrids comprising pyrazole and acetylisoxazoline were prepared from (R)-carvone and characterized by technique spectroscopies Nuclear Magnetic Resonance (NMR), IR and High-Resolution Mass Spectrometry. Density Functional Theory (DFT) determined the structural parameters. Their cytotoxic activity was evaluated in vitro against four human cancer cell lines. Methods & results: All the studied semi and thiosemicarbazone demonstrate a promising potential as anticancer agents. The mechanism of action of these compounds involves apoptosis in HT-1080 cells, supported by an increase in the level of caspase-3/7 activity, which also arrests the cell cycle in the G0/G1 phase. Molecular docking studies were performed to establish the potential of the most active compounds 4a and 5a . ADMET analysis showed appropriate pharmacokinetic properties, allowing structure prediction for anticancer activity.
Databáze: MEDLINE