title: Novel Improved Synthesis of HSP70 Inhibitor, Pifithrin-μ. In Vitro Synergy Quantification of Pifithrin-μ Combined with Pt Drugs in Prostate and Colorectal Cancer Cells.
abstract: We describe a novel improved approach to the synthesis of the important and well-known heat shock protein 70 inhibitor (HSP70), pifithrin-μ, with corresponding and previously unreported characterisation. The first example of a combination study comprising HSP70 inhibitor pifithrin-μ and cisplatin or oxaliplatin is reported. We have determined, using the Chou-Talalay method, (i) moderate synergistic and synergistic effects in co-treating PC-3 prostate cancer cells with pifithrin-μ and cisplatin and (ii) significant synergistic effects including strong synergism in cotreating HT29 colorectal cancer cells with oxaliplatin and pifithrin-μ.
authors.affiliation: Centre for Synthesis and Chemical Biology, Department of Pharmaceutical and Medicinal Chemistry, Royal College of Surgeons in Ireland, 123 St. Stephens Green, Dublin 2 D02 YN77, Ireland. aoifemckeon@rcsi.ie.
authors.forename: Aoife M
authors.initials: AM
authors.lastname: McKeon
authors.affiliation: Shannon ABC, South Campus, IT Tralee, Clash, Tralee, Co., Kerry V92 CX88, Ireland. ae12@hw.ac.uk.
authors.forename: Alan
authors.initials: A
authors.lastname: Egan
authors.affiliation: Centre for Synthesis and Chemical Biology, Department of Pharmaceutical and Medicinal Chemistry, Royal College of Surgeons in Ireland, 123 St. Stephens Green, Dublin 2 D02 YN77, Ireland. jaychandanshive@rcsi.ie.
authors.forename: Jay
authors.initials: J
authors.lastname: Chandanshive
authors.affiliation: Shannon ABC, South Campus, IT Tralee, Clash, Tralee, Co., Kerry V92 CX88, Ireland. helena.mcmahon@staff.ittralee.ie.
authors.forename: Helena
authors.initials: H
authors.lastname: McMahon
authors.affiliation: Centre for Synthesis and Chemical Biology, Department of Pharmaceutical and Medicinal Chemistry, Royal College of Surgeons in Ireland, 123 St. Stephens Green, Dublin 2 D02 YN77, Ireland. dgriffith@rcsi.ie.
authors.forename: Darren M
authors.initials: DM
authors.lastname: Griffith
keywords: Chou-Talalay method; cancer; combination study; heat shock protein 70; pifithrin-μ; platinum; synthesis