Anti-Cancer Discovery & Therapy   (Track)

NEW SERIES OF ACRIDINES-BASED COMPOUNDS AS DUAL INHIBITORS OF TOPOISOMERASE I AND II AND GROWTH INHIBITION OF HL-60CELLS

Othman Salem, Jana Janočková, Mária Vilková, Michal Bečka, Jana Kaspárková, Viktor Brabec, Rastislav Jendzelovský, Ján Imrich, Peter Fedoročko and Mária Kozurkováa

Department of Biochemistry, Faculty of Science, Pavla Jozefa Shafarika University, Kosice, Slovakia

Abstract

As the costs of testing and licensing new drugs continue to rise, many researchers believe that it would be more cost effective to reinvestigate and improve drugs which are already on the market. One example of a widely available drug group which could be reassessed in this manner would be acridine derivatives. This is of considerable interest to our work in developing DNA topoisomerase inhibitors as chemotherapeutic agents [1]. To date, only a small group of dual acridine inhibitors of topoisomerases I and II have been described in detail. In this study, a newly synthesized series of acridine derivatives, compounds 1-5, is described and their biological activity on HL-60 cell lines is assessed using different techniques. Binding studies were also performed between the derivatives and DNA in order to characterize the mechanism of the agents' effect in more detail. The results of UV-vis absorption spectroscopy prove that the binding of derivatives 1-5 occurs with a binding constant value of K = 2.7×104-7.8×104 M-1. These findings are indicative of a strong interaction between the derivatives and DNA, and this hypothesis is supported by the results of the fluorescence emission, LD and viscometric assays.

REFERENCES

[1] J. Janočková, J. Plšíková, J. Kašpárková, V. Brabec, R. Jendželovský, J. Mikeš, J. Kovaľ, S. Hamuľaková, P. Fedoročko, K. Kuča, M. Kožurková, Eur. J. Pharm. Sci, 76, 192-202, 2015