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N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry
Siberian Branch of Russian Academy of Science

The paper of NIOCh's researchers Kseniya Kovaleva, Olga Yarovaya and Nariman Salakhutdinov  is published in the journal  Journal of Natural Products,  (IF 4,257I

Dehydroabietylamine Ureas and Thioureas as Tyrosyl-DNA Phosphodiesterase 1 Inhibitors That Enhance the Antitumor Effect of Temozolomide on Glioblastoma Cells

Kseniya Kovaleva, Olga Oleshko, Evgeniya Mamontova, Olga Yarovaya, Olga Zakharova, Alexandra Zakharenko, Alena Kononova, Nadezhda Dyrkheeva, Sergey Cheresiz, Andrey Pokrovsky, Olga Lavrik, Nariman Salakhutdinov

Journal of Natural Products, 2019, V. 82, N 9, Pp 2443-2450  

DOI: https://doi.org/10.1021/acs.jnatprod.8b01095




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.