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Design, Synthesis, and Evaluation of ω‐(Isothiocyanato)alkylphosphinates and Phosphine Oxides as Antiproliferative Agents
Author(s) -
Janczewski Łukasz,
Psurski Mateusz,
Świtalska Marta,
Gajda Anna,
Goszczyński Tomasz M.,
Oleksyszyn Józef,
Wietrzyk Joanna,
Gajda Tadeusz
Publication year - 2018
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201700619
Subject(s) - phosphinate , sulforaphane , benzyl isothiocyanate , chemistry , hl60 , apoptosis , phosphine , in vivo , isothiocyanate , cell culture , in vitro , biological activity , mechanism of action , biochemistry , stereochemistry , pharmacology , organic chemistry , biology , genetics , microbiology and biotechnology , fire retardant , catalysis
A series of 21 novel, structurally diverse ω‐(isothiocyanato)alkylphosphinates and phosphine oxides (ITCs) were designed and synthesized in moderate to good yields. The synthesized compounds were evaluated for in vitro antiproliferative activity using LoVo and LoVo/DX cancer cell lines. The biological activity of the synthesized compounds was higher than that of natural isothiocyanates such as benzyl isothiocyanate or sulforaphane. The antiproliferative activity of selected ITCs was also tested on selected cancer cell lines: A549, MESSA and MESSA/DX‐5, HL60 and HL60MX2, BALB/3T3, and 4T1. These compounds were assessed for their mechanism of action as inducers of cell‐cycle arrest and apoptosis. Ethyl (6‐isothiocyanatohexyl)(phenyl)phosphinate ( 71 ) was tested in vivo on the 4T1 cell line and demonstrated moderate antitumor activity, similar to that benzyl isothiocyanate and cyclophosphamide.