Improving the anticancer activity of fluorinated glucosamine and galactosamine analogs by attachment of a ferrocene or ruthenium tetrazene motif

0583649 - ÚCHP 2025 RIV US eng J - Článek v odborném periodiku
Hamala, Vojtěch - Ondrášková, K. - Červenková Šťastná, Lucie - Krčil, Aleš - Müllerová, Monika - Kurfiřt, Martin - Hiršová, Kateřina - Holčáková, J. - Gyepes, R. - Císařová, I. - Bernášková, Jana - Hrstka, R. - Karban, Jindřich
Improving the anticancer activity of fluorinated glucosamine and galactosamine analogs by attachment of a ferrocene or ruthenium tetrazene motif.
Applied Organometallic Chemistry. (2024), č. článku e7399. ISSN 0268-2605. E-ISSN 1099-0739
Grant CEP: GA MŠMT(CZ) LTC20052
Grant ostatní: MEYS(XE) CA18103
Institucionální podpora: RVO:67985858
Klíčová slova: antitumor * cytotoxicity * ferrocene * apoptosis
Obor OECD: Inorganic and nuclear chemistry
Impakt faktor: 3.9, rok: 2022
Způsob publikování: Open access

Acylated N-acetyl hexosamine hemiacetals are known for their cytotoxicity. We have previously reported that cytotoxicity can be increased by replacing
one or more acyloxy groups with fluorine. Herein, we present the synthesis of 4,6-difluorinated D-gluco- and 4-fluorinated D-galacto-configured hexosaminederived glycoconjugates with organoruthenium or ferrocene complexes and their in vitro cytotoxicity against three cancer cell lines (A2780, SK-OV-3, and MDA-MB-231) and one noncancerous cell line (HEK-293). The attachment of the organometallic moiety at the 2-position significantly enhanced the cytotoxicity, especially against triple-negative MDA-MB-231 and the cisplatin resistant SK-OV-3 cancer cells. We observed a clear significance of an unprotected and acetyl protected anomeric hydroxyl for the cytotoxicity. Glycoconjugates with a non-hydrolysable organic or organometallic group at the anomeric position were generally nontoxic. A more detailed analysis revealed that, in particular, complexes with the ruthenium tetrazene complex induced apoptosis in both SK-OV-3 and MDA-MB-231 cells, as demonstrated by western blot analysis and Annexin V-FITC/PI staining. The structures of the two most cytotoxic organoruthenium and ferrocene glycoconjugates were confirmed by X-ray diffraction analysis.
Trvalý link: https://hdl.handle.net/11104/0351673