Poster Presenter

Amidinoanthracyclines - A New Hope For Anticancer And Anti-HCV Therapy
M. Lukawska,. I. Oszczapowicz ., P. Borowicz., A. Boguszewska-Chachulska ., J. Oszczapowicz
Poland

Anthracyclines are antitumor drugs with wide spectrum of activity in human cancers. However, their clinical effectiveness is limited by several factors, including dose-dependent toxicity, cardiotoxicity and increasing the resistance of tumor cells to this drugs.

Hepatitis C virus (HCV) infections are one of the major health problems because the current therapy is effective in only 50 - 80% of cases. It is known that some anthracyclines demonstrate antihelicase activity.

Amidinoanthracyclines - a new group of anthracycline derivatives containing the amidino group instead of the amino group at the position 3'of the daunosamino moiety - display in comparison to the parent anthracyclines, much lower toxicity, (LD50 even 60 fold higher), lower cardiotoxicity, the possibility to overcome the drug resistance of cancer cells. Additionally, some of them exhibit much higher antiproliferative activity.

The tests using the high throughput fluorometric HCV helicase assay show that these derivatives exhibit appreciable antihelicase activity (the IC50 values in the range of 0.03-11.32 micromole. The tests in the subgenomic HCV replicon system made for selected amidinoanthracyclines resulted in therapeutic indices (SI) in the range from 5.7 to 33.3.

These results indicate that introduction of the amidino group into the anthracycline molecules is a promising way to improve their properties, and that amidinoanthracyclines may be considered as potential anticancer and anti-HCV drugs.