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Anticancer Properties of 3-Dietoxyphosphorylfuroquinoline-4,9-dione.

Joanna Drogosz-StachowiczKatarzyna Gach-JanczakMarek MirowskiPietrzak JacekTomasz JaneckiAnna Janecka
Published in: Molecules (Basel, Switzerland) (2023)
Herein, the antitumor activity of a novel synthetic analog with 5,8-quinolinedione scaffold, diethyl (2-(2-chlorophenyl)-4,9-dioxo-4,9-dihydrofuro [3,2- g ]quinolin-3-yl)phosphonate ( AJ-418 ) was investigated on two breast cancer cell lines. This analog was selected from a small library of synthetic quinolinediones on the basis of its strong antiproliferative activity against MCF-7 and MDA-MB-231 cells and 4-5-fold lower cytotoxicity towards healthy MCF-10A cells. The morphology of MCF-7 and MDA-MB-231 cancer cells treated with AJ-418 changed drastically, while non-tumorigenic MCF-10A cells remained unaffected. In MCF-7 cells, after 24 h incubation, the increased number of apoptotic cells coincided with a decrease in proliferation and cell viability. The 24 h treatment of MDA-MB-231 cells with the tested compound reduced their cell viability and proliferation rate; however, a significant pro-apoptotic effect was visible only after longer incubation times (48 h and 72 h). Then, the maximum tolerated dose (MTD) of compound AJ-418 in C3H mice after subcutaneous administration was determined to be 160 mg/kg, showing that this analog was well tolerated and can be further evaluated to assess its potential therapeutic effect in tumor-bearing mice.
Keyphrases
  • cell cycle arrest
  • induced apoptosis
  • breast cancer cells
  • cell death
  • signaling pathway
  • type diabetes
  • high resolution
  • smoking cessation
  • combination therapy
  • insulin resistance
  • single molecule