Semicarbazone, thiosemicarbazone tailed isoxazoline-pyrazole: synthesis, DFT, biological and computational assessment.
Abdoullah BimoussaMouhi Eddine HachimKhalil El KhatabiYassine LaamariAli OubellaMohamed F AlAjmiAziz AuhmaniMohammed Aziz AjanaHamid MorjaniMy Youssef Ait IttoPublished in: Future medicinal chemistry (2024)
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.
Keyphrases
- molecular docking
- cell cycle
- density functional theory
- magnetic resonance
- cell cycle arrest
- induced apoptosis
- high resolution mass spectrometry
- molecular dynamics simulations
- cell death
- endoplasmic reticulum stress
- molecular dynamics
- cell proliferation
- liquid chromatography
- endothelial cells
- oxidative stress
- human health
- pi k akt
- high resolution
- solid state
- induced pluripotent stem cells
- gas chromatography
- mass spectrometry
- contrast enhanced
- risk assessment
- squamous cell carcinoma
- computed tomography
- climate change
- data analysis
- pluripotent stem cells