Synthesis of new poly(N-vinyl pyrrolidone-co-maleic acid) -: Peptide hormone conjugates with anticancer activity

Gonadotropin releasing hormone (GnRH) is a decapeptide regulating the gonadotropin release in organisms. Its analogues inhibit breast, endometrium and prostatic tumor cell proliferation in vitro. Some analogues were conjugated via the lysine side chain to poly(N-vinyl pyrrolidone-co-maleic acid) using biodegradable and non-biodegradable oligopeptide spacers. The conjugates were prepared by acylation of oligopeptide nitrophenyl esters with the polymeric precursor, poly(N-vinyl pyrrolidone-co-maleic anhydride), by reacting the GnRH analogues with the polymeric active ester. In vitro tests of these products exhibited increased effects on MCF-7 and MDA MB-231 breast, Ishikawa endometrium and PC3 prostatic human tumor cells compared with the parent decapeptides.