New hyaluronan-terpyridine conjugate: Metal complexes and their biological activity

Terpyridine coordination compounds have attracted broad interest concerning their biomedical applications. We devised a terpyridine-hyaluronic acid conjugate and studied its copper(II), iron(II) and zinc(II) metal complexes. We determined the antiproliferative activities of the ligand and the metal complexes in human cell lines A2780 (ovary, adenocarcinoma), A549 (lung, carcinoma), MDA-MB-453 (breast, carcinoma), SKHep1 (liver, carcinoma) and compared them to 4 '-Chloro-2,2 ':6 ',2 ''-terpyridine systems. The terpyridine-hyaluronan conjugate showed pharmacologically significant antiproliferative activity in all cell lines tested. The ternary metal complexes of terpyridine-hyaluronan conjugate and 4-chloro-terpyridine showed significant IC50 values (nanomolar range) depending on the cell line. Additionally, Cu2+ and Zn2+ ternary complexes exhibited higher antiproliferative activity than Doxorubicin.