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

• Published in: Bioorganic & medicinal chemistry letters 2018-08, Vol.28 (15), p.2611-2615
• Main Authors: Psurski, Mateusz, Janczewski, Łukasz, Świtalska, Marta, Gajda, Anna, Goszczyński, Tomasz M., Ciekot, Jarosław, Winiarski, Łukasz, Oleksyszyn, Józef, Wietrzyk, Joanna, Gajda, Tadeusz
• Format: Article
• Language: English
• Subjects: Antiproliferative activity; Cytostatic activity; Isothiocyanate; Mercapturic acid; Proapoptotic activity; Synthesis
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2018.06.042

[Display omitted] •A series of phosphorus-containing isothiocyanate-derived mercapturic acids with high antiproliferative potency was obtained.•In 1H and 31P NMR studies, a presence of a mixture of rotamers was confirmed.•Representative compounds were recognized as moderate apoptosis inducers that do not affect cell cycle progression. 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.