Letters in Drug Design & Discovery

G. Perry
University of Texas
San Antonio, TX
USA
Email: lddd@benthamscience.org

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The Disulfide Analogues of Isophosphoramide Mustard for Anticancer Therapy

Author(s): Joanna Cytarska, Krzysztof Skowerski, Szymon Jaworski, Konrad Misiura, Beata Filip-Psurska, Joanna Wietrzyk.

Graphical Abstract:


Abstract:

Novel disulfide analogues of isophosphoramide mustard (iPAM) were designed and synthesised. All compounds were hydrolytically stable and underwent reduction by L-glutathione with different kinetic parameters. Based on the HPLC-MS analysis a mechanism of activation by glutathione obtained disulfide analogues of iPAM was proposed. The compounds were tested for cytotoxic activity against human promyelocytic leukaemia HL-60, human lymphoblastic leukaemia MOLT-4, human lymphoblastic leukaemia CCRF/CEM, human bladder cancer HCV29T, murine melanoma B16-F0 and murine fibroblasts Balb3T3 cell lines. The most promising anticancer activity was exhibited by compound 4, which proved to be more active than the reference cisplatin against all cancer cell lines.

Keywords: Anticancer activity, disulfide, glutathione, isophosphoramide mustard.

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Article Details

VOLUME: 12
ISSUE: 3
Year: 2015
Page: [172 - 179]
Pages: 8
DOI: 10.2174/1570180811666141010001007
Price: $58