2. Academic Validation
  3. Phosphorus-containing isothiocyanate-derived mercapturic acids as a useful alternative for parental isothiocyanates in experimental oncology

Phosphorus-containing isothiocyanate-derived mercapturic acids as a useful alternative for parental isothiocyanates in experimental oncology

  • Bioorg Med Chem Lett. 2018 Aug 15;28(15):2611-2615. doi: 10.1016/j.bmcl.2018.06.042.
Mateusz Psurski 1,  Łukasz Janczewski 2,  Marta Świtalska 3,  Anna Gajda 2,  Tomasz M Goszczyński 3,  Jarosław Ciekot 3,  Łukasz Winiarski 4,  Józef Oleksyszyn 4,  Joanna Wietrzyk 3,  Tadeusz Gajda 2
Affiliations

Affiliations

  • 1 Department of Experimental Oncology, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 12 Weigla St., 53-114 Wrocław, Poland. Electronic address: mateusz.psurski@iitd.pan.wroc.pl.
  • 2 Institute of Organic Chemistry, Faculty of Chemistry, Technical University of Lodz, 116 Żeromskiego St., 90-924 Łódź, Poland.
  • 3 Department of Experimental Oncology, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 12 Weigla St., 53-114 Wrocław, Poland.
  • 4 Division of Medicinal Chemistry and Microbiology, Faculty of Chemistry, Wrocław University of Science and Technology, 27 Wybrzeże Wyspiańskiego St., 50-370 Wrocław, Poland.
PMID: 29945793 DOI: 10.1016/j.bmcl.2018.06.042
Abstract

A series of phosphonates, phosphinates and phosphine oxides isothiocyanate-derived mercapturic acids were synthesized. A temperature dependence dynamic proton decoupled 31P NMR studies indicated that in most cases the compounds were obtained as a mixture of rotamers. Moreover, biologically relevant reversibility of mercapturic acids synthesis from the parental isothiocyanates was confirmed. All compounds were evaluated ashighly active antiproliferative agents in vitro in human colon Cancer cell lines (LoVo and its doxorubicin-resistant subline LoVo/DX). The cell cycle progression and Caspase-3 activity analyses revealed compounds moderate activity as Apoptosis inducers and their poor influence on cell cycle progression in the LoVo cells. Our results confirm that isothiocyanate-derived mercapturic acids present a reasonable alternative for the parental compounds, and can replace them in the future studies on isothiocyanates potential as Anticancer agents.

Keywords

Antiproliferative activity; Cytostatic activity; Isothiocyanate; Mercapturic acid; Proapoptotic activity; Synthesis.

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