Synthesis and Biological Evaluation of Distamycin Analogues – New Potential Anticancer Agents |
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| Authors: | Danuta Drozdowska Malgorzata Rusak Wojciech Miltyk Krystyna Midura‐Nowaczek |
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| Affiliation: | 1. Department of Haematological Diagnostics, Medical University, Bia?ystok, Poland;2. Laboratory of Drug Analysis, Medical University, Bia?ystok, Poland;3. Department of Organic Chemistry, Medical University, Bia?ystok, Poland. Fax: +48 85 748‐5416 |
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| Abstract: | Eight of analogues of distamycin, potential minor‐groove binders, were synthesized and tested for in‐vitro cytotoxicity towards human breast cancer cells MCF‐7 and MDA‐MB‐231. The method of synthesis is simple and convenient. All of the compounds 1 – 8 showed antiproliferative and cytotoxic effects against both cell lines in the range 3.47 to 12.53 μM for MDA‐MB‐231 and 4.35 to 12.66 μM for MCF‐7. All compounds demonstrated activity against DNA topoisomerases I and II at a concentration of 50 μM. The ethidium bromide assay showed that these compounds bind to plasmid pBR322, yet weaker than distamycin. Further investigations concerning the mechanism of cytotoxicity are now in progress, but the IC50 values suggest that synthetic distamycin analogues with a free amino group, 3 – 4 and 7 – 8 , can serve as potential carriers of strong acting elements, e. g. alkylating groups. |
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| Keywords: | Cytotoxic activity Anticancer activity Distamycin analogue DNA binding DNA topoisomerase |
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