Dehydroabietylamine Ureas and Thioureas as Tyrosyl-DNA Phosphodiesterase 1 Inhibitors That Enhance the Antitumor Effect of Temozolomide on Glioblastoma Cells.
Kseniya KovalevaOlga OleshkoEvgeniya MamontovaOlga I YarovayaOlga ZakharovaAlexandra ZakharenkoAlena KononovaNadezhda DyrkheevaSergey CheresizAndrey PokrovskyOlga LavrikNariman SalakhutdinovPublished in: Journal of natural products (2019)
A new class of tyrosyl-DNA phosphodiesterase 1 (TDP1) inhibitors was found among resin acid derivatives. Several novel ureas and thioureas derived from dehydroabietylamine were synthesized and tested for TDP1 inhibition. The synthesized compounds showed IC50 values in the range of 0.1 to 3.7 μM and demonstrated low cytotoxicity against the human tumor cell lines U-937, U-87MG, MDA-MB, SK-Mel8, A-549, MCF7, T98G, and SNB19. Several compounds showed enhancement of the cytotoxic activity of the alkylating agent temozolomide, which is used as a first line therapy against glioblastoma (GBM), in the GBM cell lines U-87MG and SNB19.
Keyphrases
- circulating tumor
- cell cycle arrest
- breast cancer cells
- cell free
- induced apoptosis
- single molecule
- endothelial cells
- amyotrophic lateral sclerosis
- newly diagnosed
- nucleic acid
- cell death
- induced pluripotent stem cells
- pi k akt
- pluripotent stem cells
- signaling pathway
- circulating tumor cells
- oxide nanoparticles
- stem cells
- smoking cessation