A series of pentamethinium salts with benzothiazolium and indolium side units comprising one or two positive charges were designed and synthesized to determine the relationships among the molecular structure, charge density, affinity to sulfated polysaccharides, and biological activity. Firstly, it was found that the affinity of the pentamethinium salts to sulfated polysaccharides correlated with their biological activity. Secondly, the side heteroaromates displayed a strong effect on the cytotoxicity and selectivity towards cancer cells. Finally, doubly charged pentamethinium salts possessing benzothiazolium side units exhibited remarkably high efficacy against a taxol-resistant cancer cell line.

1st Faculty of Medicine Charles University Prague Kateřinská 32 121 08 Prague 2 Czech Republic

Institute of Molecular and Translational Medicine Hněvotínská 5 779 00 Olomouc Czech Republic

Institute of Molecular Genetics Academy of Sciences of the Czech Republic Vídeňská 1083 142 20 Prague 4 Czech Republic

University of Chemistry and Technology Prague Technická 5 166 28 Prague 6 Czech Republic

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$a Pentamethinium salts as ligands for cancer: Sulfated polysaccharide co-receptors as possible therapeutic target / $c T. Bříza, J. Králová, S. Rimpelová, M. Havlík, R. Kaplánek, Z. Kejík, P. Martásek, I. Mikula, P. Džubák, M. Hajdúch, T. Ruml, V. Král,

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$a A series of pentamethinium salts with benzothiazolium and indolium side units comprising one or two positive charges were designed and synthesized to determine the relationships among the molecular structure, charge density, affinity to sulfated polysaccharides, and biological activity. Firstly, it was found that the affinity of the pentamethinium salts to sulfated polysaccharides correlated with their biological activity. Secondly, the side heteroaromates displayed a strong effect on the cytotoxicity and selectivity towards cancer cells. Finally, doubly charged pentamethinium salts possessing benzothiazolium side units exhibited remarkably high efficacy against a taxol-resistant cancer cell line.

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$a Havlík, Martin $u University of Chemistry and Technology, Prague, Technická 5, 166 28, Prague 6, Czech Republic; First Faculty of Medicine, Charles University in Prague, Kateřinská 32, 121 08, Prague 2, Czech Republic.

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$a Kaplánek, Robert $u University of Chemistry and Technology, Prague, Technická 5, 166 28, Prague 6, Czech Republic; First Faculty of Medicine, Charles University in Prague, Kateřinská 32, 121 08, Prague 2, Czech Republic.

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$a Kejík, Zdeněk $u First Faculty of Medicine, Charles University in Prague, Kateřinská 32, 121 08, Prague 2, Czech Republic.

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