Journal
JOURNAL OF NATURAL PRODUCTS
Volume 82, Issue 9, Pages 2443-2450Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.jnatprod.8b01095
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Funding
- Foundation by the Russian Foundation Research [18-33-00297]
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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 mu M and demonstrated low cytotoxicity against the human tumor cell lines U-937, U-87MG, MDA-MB, SK-Me18, 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.
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