| Autor: |
Rykowski S; Institute of Medical Biology, Polish Academy of Sciences, Łódź, Poland., Gurda-Woźna D; Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznan, Poland., Fedoruk-Wyszomirska A; Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznan, Poland., Orlicka-Płocka M; Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznan, Poland., Kowalczyk A; Department of Molecular Microbiology, Faculty of Biology and Environmental Protection, University of Lodz, Łódź, Poland., Stączek P; Department of Molecular Microbiology, Faculty of Biology and Environmental Protection, University of Lodz, Łódź, Poland., Denel-Bobrowska M; Institute of Medical Biology, Polish Academy of Sciences, Łódź, Poland., Biniek-Antosiak K; Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznan, Poland., Rypniewski W; Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznan, Poland., Wyszko E; Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznan, Poland., Olejniczak AB; Institute of Medical Biology, Polish Academy of Sciences, Łódź, Poland. |
| Abstrakt: |
The synthesis of carborane-1,8-naphthalimide conjugates and evaluation of their DNA-binding ability and anticancer activity were performed. A series of 4-carboranyl-3-nitro-1,8-naphthalimide derivatives, mitonafide and pinafide analogs, were synthesised via amidation and reductive amination reactions, and their calf thymus DNA (ct-DNA)-binding properties were investigated using circular dichroism, UV-vis spectroscopy, and thermal denaturation. Results showed that conjugates 34 - 37 interacted very strongly with ct-DNA (Δ T m = 10.00-13.00 °C), indicating their ability to intercalate with DNA, but did not inhibit the activity of topoisomerase II. The conjugates inhibited the cell growth of the HepG2 cancer cell line in vitro . The same compounds caused the G2M phase arrest. Cell lines treated with these conjugates showed an increase in reactive oxygen species, glutathione, and Fe 2+ levels, lipid peroxidation, and mitochondrial membrane potential relative to controls, indicating the involvement of ferroptosis. Furthermore, these conjugates caused lysosomal membrane permeabilization in HepG2 cells but not in MRC-5 cells. |
