In the search for new anticancer agents we designed and synthesized batracylin derivatives with linking synthetic amino acid side chains of different lengths and adenosine. Unexpectedly, we have found that in water and the culture media adenosine–amino acid–BAT conjugates form supramolecular structures and this prevents these compounds from entering cells. Consequently, these compounds exerted no biological activity when tested towards two human cell lines, lung adenocarcinoma (A549) and human leukemia (HL-60). In contrast, several amino acid–BAT precursors showed up to 25-fold enhanced cytotoxic activity compared to BAT and these compounds strongly interfered with DNA topoisomerase II activity and its cellular functions. In particular, these conjugates inhibited centromere segregation during mitosis in drug-treated tumor cells by preventing topoisomerase II-dependent Aurora B activation.
Authors
- mgr inż. Wioleta Januchta link open in new tab ,
- dr inż. Marcin Serocki link open in new tab ,
- prof. dr hab. inż. Krystyna Dzierzbicka link open in new tab ,
- dr hab. inż. Grzegorz Cholewiński link open in new tab ,
- dr inż. Monika Gensicka-Kowalewska link open in new tab ,
- prof. dr hab. inż. Andrzej Składanowski link open in new tab
Additional information
- DOI
- Digital Object Identifier link open in new tab 10.1039/c6ra04957e
- Category
- Publikacja w czasopiśmie
- Type
- artykuł w czasopiśmie wyróżnionym w JCR
- Language
- angielski
- Publication year
- 2016
