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

Dalton Trans. 2016 Aug 16;45(33):13038-41. doi: 10.1039/c6dt01510g.

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)].

MeSH terms

  • Antineoplastic Agents* / chemistry
  • Antineoplastic Agents* / pharmacology
  • Cell Line
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Humans
  • Peptides* / chemistry
  • Peptides* / pharmacology
  • Platinum* / chemistry
  • Platinum* / pharmacology
  • Proteins* / chemistry
  • Proteins* / pharmacology

Substances

  • Antineoplastic Agents
  • Peptides
  • Proteins
  • buforin II
  • Platinum