511530-02-2Relevant academic research and scientific papers
Synthesis and biological evaluation of novel analogues of batracylin with synthetic amino acids and adenosine: An unexpected effect on centromere segregation in tumor cells through a dual inhibition of topoisomerase IIα and Aurora B
Januchta, Wioleta,Serocki, Marcin,Dzierzbicka, Krystyna,Cholewinski, Grzegorz,Gensicka, Monika,Skladanowski, Andrzej
, p. 42794 - 42806 (2016)
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.
Synthesis and cytotoxic activity of conjugates of muramyl and normuramyl dipeptides with batracylin derivatives
Dzierzbicka, Krystyna,Trzonkowski, Piotr,Sewerynek, Przemys?aw,My?liwski, Andrzej
, p. 978 - 986 (2007/10/03)
The synthesis of MDP (muramyl dipeptide) or nor-MDP (normuramyl dipeptide) conjugates modified at the peptide part with batracylin (BAT) or batracylin derivatives is described. Batracylin was synthesized by our modified method (Scheme 3). The synthesis of BAT via this modified route now appears to be feasible on a multigram scale. Preliminary screening data obtained at the National Cancer Institute (NCI, Bethesda, MD) have revealed that the conjugates did not expose any cytotoxic activity even at 10-4-10-8 M or μg/mL. During tests performed at Medical University of Gdansk, Poland, two analogues 11c and 11e reduced the proliferation of Ab melanoma cells in vitro compared with batracylin alone (Table 2, Figure 1).
