Synthesis and characterisation of a novel mono functionalisable Pt(IV) oxaliplatin-type complex and its peptide conjugate

[Display omitted] •Synthesis of a novel mono functionalisable Pt(IV) oxaliplatin type complex.•Successful conjugation of a tumour targeting peptide, TPP.•Enhanced in vitro cytotoxicity against colorectal cancer cells. The synthesis and characterisation of a novel Pt(IV) monocarboxy precursor complex...

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Bibliographic Details
Published in:Inorganica Chimica Acta 2020-05, Vol.505, p.119492, Article 119492
Main Authors: Kitteringham, Eolann, McKeon, Aoife M., O'Dowd, Paul, Devocelle, Marc, Murphy, Brona M., Griffith, Darren M.
Format: Article
Language:English
Subjects:
Biotechnology
Cancer
Colorectal cancer
Conjugates
Conjugation
Cytotoxicity
Functionalisation
HSP70
Oxaliplatin: tumour penetrating peptide
Peptides
Platinum
Synthesis
Toxicity
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Summary:[Display omitted] •Synthesis of a novel mono functionalisable Pt(IV) oxaliplatin type complex.•Successful conjugation of a tumour targeting peptide, TPP.•Enhanced in vitro cytotoxicity against colorectal cancer cells. The synthesis and characterisation of a novel Pt(IV) monocarboxy precursor complex c,c,t-[Pt(DACH)(Ox)(OEt)(Suc)], which can be employed to synthesise mono functionalised Pt(IV) oxaliplatin-based complexes is reported. Reaction of c,c,t-[Pt(DACH)(Ox)(OEt)(Suc)] with a tumour penetrating peptide, TPP, afforded the corresponding novel monofunctionalised Pt(IV) peptide conjugate c,c,t-[Pt(DACH)(Ox)(OEt)(SucTPP)] in high purity. Conjugation of TPP to c,c,t-[Pt(DACH)(Ox)(OEt)(Suc)] was demonstrated to ameliorate its inherent cytotoxicity fifteen fold in the Pt sensitive HCT116 colorectal cancer cell line and two fold in the relatively resistant HT29 colorectal cancer cell line.
ISSN:0020-1693
1873-3255
DOI:10.1016/j.ica.2020.119492