Synthesis and anticancer cytotoxicity with structural context of an α-hydroxyphosphonate based compound library derived from substituted benzaldehydes

Zita Rádai, Tímea Windt, Veronika Nagy, András Füredi, Nóra Zsuzsa Kiss, Ivan Ranelović, József Tóvári, György Keglevich, Gergely Szakács, Szilárd Tóth

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

We synthesized substituted benzaldehyde derived α-hydroxyphosphonates (αOHP), α-hydroxyphosphonic acids (αOHPA) and α-phosphinoyloxyphosphonates (αOPP) and characterized their cytotoxicity against a panel of cancer cell lines. A library containing 56 analogues was screened against Mes-Sa parental and Mes-Sa/Dx5 multidrug resistant uterine sarcoma cell lines, using a fluorescence-based cytotoxicity assay. The cytotoxicity screening revealed that dibenzyl-αOHPs and dimethyl-α-diphenyl-OPPs were the most active clusters, which encouraged us to synthesize further dibenzyl-α-diphenyl-OPP derivatives that elicited pronounced cell killing. Further structure-activity relationships showed the relevance of hydrophobicity and the position of substituents on the main benzene ring as determinants of toxicity. The most active analogs proved to be equally, or even more toxic to the multidrug resistant (MDR) cell line Mes-Sa/Dx5, suggesting these compounds may overcome P-glycoprotein mediated multidrug resistance by evading the drug transporter.

Original languageEnglish
Pages (from-to)14028-14035
Number of pages8
JournalNew Journal of Chemistry
Volume43
Issue number35
DOIs
Publication statusPublished - 2019

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Materials Chemistry

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