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

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Authors

HAMALA Vojtech ONDRÁŠKOVÁ Kateřina STASTNA Lucie Cervenkova KRCIL Ales MULLEROVA Monika KURFIRT Martin HIRSOVA Katerina HOLCAKOVA Jitka GYEPES Robert CISAROVA Ivana BERNASKOVA Jana HRSTKA Roman KARBAN Jindrich

Year of publication 2024
Type Article in Periodical
Magazine / Source Applied Organometallic Chemistry
MU Faculty or unit

Faculty of Science

Citation
Doi http://dx.doi.org/10.1002/aoc.7399
Keywords antitumor; apoptosis; cytotoxicity; ferrocene; fluorinated carbohydrates; organometallic; ruthenium
Attached files
Description 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 hexosamine-derived 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.
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