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

• Published in: Molecules (Basel, Switzerland) Switzerland), 2023-03, Vol.28 (7), p.3128
• Main Authors: Drogosz-Stachowicz, Joanna, Gach-Janczak, Katarzyna, Mirowski, Marek, Pietrzak, Jacek, Janecki, Tomasz, Janecka, Anna
• Format: Article
• Language: English
• Subjects: Animals; Antimitotic agents; Antineoplastic agents; Antineoplastic Agents - pharmacology; Antitumor activity; Apoptosis; Bioavailability; Breast cancer; Breast Neoplasms; Cancer; Cancer therapies; Care and treatment; Cell cycle; Cell growth; Cell Line, Tumor; Cell Proliferation; Cell viability; Cytology; cytotoxic activity; Cytotoxicity; DNA damage; Drug dosages; Female; Humans; Leukemia; maximum tolerated dose; MCF-7 Cells; Mice; Mice, Inbred C3H; Morphology; Phosphonates; Phosphorus; Phosphorylation; Quinoline; quinolinediones; Stains & staining; Testing; Tumor cell lines
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules28073128

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- ]quinolin-3-yl)phosphonate ( ) 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 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 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.