Derivatisation of buforin IIb, a cationic henicosapeptide, to afford its complexation to platinum(ii) resulting in a novel platinum(ii)–buforin IIb conjugate with anti-cancer activity

Abstract

Herein we report the synthesis of buforin IIb, its novel malonate derivative malBuf and its Pt(II) complex cis-[Pt(NH₃)₂(malBuf_–2H)]. We decided to harness the cell targeting, cell-penetrating and anti-proliferative effects of buforin IIb to help target a cytotoxic dose of a Pt DNA binding species, {Pt(NH₃)₂} to cancer cells whilst also delivering a peptide with potent anti-cancer properties. Preliminary in vitro data shows cis-[Pt(NH₃)₂(malBuf_–2H)] to be more cytotoxic against the cisplatin resistant ovarian cancer cell line (A2780cisR) relative to buforin IIb, cisplatin and cis-[Pt(NH₃)₂(malonate)].