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
Aoife M. McKeon,
Alan Egan,
Jay Chandanshive,
Helena McMahon,
Darren M. Griffith
Affiliations
Aoife M. McKeon
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
Alan Egan
Shannon ABC, South Campus, IT Tralee, Clash, Tralee, Co., Kerry V92 CX88, Ireland
Jay Chandanshive
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
Helena McMahon
Shannon ABC, South Campus, IT Tralee, Clash, Tralee, Co., Kerry V92 CX88, Ireland
Darren M. Griffith
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
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.
