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.
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)].
Centre for Synthesis and Chemical Biology, Department of Pharmaceutical & Medicinal Chemistry, Royal College of Surgeons in Ireland, 123 St. Stephens Green, Dublin 2, Ireland. cmarmion@rcsi.ie.
J P
JP
Parker
Centre for Synthesis and Chemical Biology, Department of Pharmaceutical & Medicinal Chemistry, Royal College of Surgeons in Ireland, 123 St. Stephens Green, Dublin 2, Ireland. cmarmion@rcsi.ie.
M
M
Devocelle
Molecular & Cellular Therapeutics, Royal College of Surgeons in Ireland, 123 St. Stephens Green, Dublin 2, Ireland.
M P
MP
Morgan
Centre for Synthesis and Chemical Biology, Department of Pharmaceutical & Medicinal Chemistry, Royal College of Surgeons in Ireland, 123 St. Stephens Green, Dublin 2, Ireland. cmarmion@rcsi.ie.
C J
CJ
Marmion
D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology; D010984:Platinum / Q000737:chemistry / Q000494:pharmacology; D011506:Proteins / Q000737:chemistry / Q000494:pharmacology
D000970:Antineoplastic Agents; D010455:Peptides; D011506:Proteins; C097849:buforin II; D010984:Platinum