Trimethyltin(IV) Bearing 3-(4-Methyl-2-oxoquinolin-1(2H)-yl)propanoate Causes Lipid Peroxidation-Mediated Autophagic Cell Death in Human Melanoma A375 Cells.
Marijana P KasalovićDušan S DimićSanja JelačaDanijela Maksimović-IvanićSanja MijatovićBojana B ZmejkovskiSimon H F SchreinerTobias RüfferNebojša Đ PantelićGoran N KaluđerovićPublished in: Pharmaceuticals (Basel, Switzerland) (2024)
A novel trimethyltin(IV) complex ( Me 3 SnL ), derived from 3-(4-methyl-2-oxoquinolin-1(2H)-yl)propanoate ligand, has been synthesized and characterized by elemental microanalysis, UV/Vis spectrophotometry, FT-IR and multinuclear ( 1 H, 13 C and 119 Sn) NMR spectroscopies. Furthermore, the structure of the ligand precursor HL was solved using SC-XRD (single-crystal X-ray diffraction). The prediction of UV/Vis and NMR spectra by quantum-chemical methods was performed and compared to experimental findings. The protein binding affinity of Me 3 SnL towards BSA was determined by spectrofluorometric titration and subsequent molecular docking simulations. Me 3 SnL has been evaluated for its in vitro anticancer activity against three human cell lines, MCF-7 (breast adenocarcinoma), A375 (melanoma) and HCT116 (colorectal carcinoma), and three mouse tumor cell lines, 4T1 (breast carcinoma), B16 (melanoma) and CT26 (colon carcinoma), using MTT and CV assays. The strong inhibition of A375 cell proliferation, ROS/RNS upregulation and robust lipid peroxidation lead to autophagic cell death upon treatment with Me 3 SnL .
Keyphrases
- cell death
- cell cycle arrest
- molecular docking
- cell proliferation
- endothelial cells
- high resolution
- magnetic resonance
- molecular dynamics
- dual energy
- pluripotent stem cells
- molecular dynamics simulations
- skin cancer
- induced pluripotent stem cells
- solid state
- computed tomography
- squamous cell carcinoma
- induced apoptosis
- pi k akt
- high throughput
- fatty acid
- signaling pathway
- image quality
- poor prognosis
- density functional theory
- magnetic resonance imaging
- breast cancer cells
- small molecule
- monte carlo
- endoplasmic reticulum stress
- protein protein
- contrast enhanced
- electron microscopy
- reactive oxygen species