19479-83-5Relevant articles and documents
Design, synthesis, and biological evaluation of a novel series of bisintercalating DNA-binding piperazine-linked bisanthrapyrazole compounds as anticancer agents
Zhang, Rui,Wu, Xing,Yalowich, Jack C.,Hasinoff, Brian B.
, p. 7023 - 7032 (2011)
A series of bisintercalating DNA binding bisanthrapyrazole compounds containing piperazine linkers were designed by molecular modeling and docking techniques. Because the anthrapyrazoles are not quinones they are unable to be reductively activated like doxorubicin and other anthracyclines and thus they should not be cardiotoxic. The concentration dependent increase in DNA melting temperature was used to determine the strength of DNA binding and the bisintercalation potential of the compounds. Compounds with more than a three-carbon linker that could span four DNA base pairs achieved bisintercalation. All of the bisanthrapyrazoles inhibited human erythroleukemic K562 cell growth in the low to submicromolar concentration range. They also strongly inhibited the decatenation activity of topoisomerase IIα and the relaxation activity of topoisomerase I. However, as measured by their ability to induce double strand breaks in plasmid DNA, the bisanthrapyrazole compounds did not act as topoisomerase IIα poisons. In conclusion, a novel group of bisanthrapyrazole compounds were designed, synthesized, and biologically evaluated as potential anticancer agents.
Double-component diazeniumdiolate derivatives as anti-cancer agents
Arutla, Viswanath,Chen, Qi,Chen, Shengxi,Hu, Qiong-Ying,Ji, Xun,Khdour, Omar
, (2020/03/13)
In this study, we synthesized a series of double-component O2-aryl diazeniumdiolate (DDNO) derivatives, of which each molecule can release up to four nitric oxide molecules. These compounds showed cytotoxic activities to cancer cells, such as human leukemia, breast cancer and lung cancer. Among them, compound 1 (DDNO-1) showed the highest specific activity to human leukemia cells. It induced cell apopotosis and arrest cell cycle of G2/M phase. The JNK and p38 protein kinases were activated by compound 1 to induce cancer cell apoptosis. Compound 1 also increased pro-apoptotic Bax level, which is a same function compared to a reported NO donor, JS-K. More interestingly, it decreased the level of an anti-apoptotic member Bcl-2, which is an opposite effect compared to JS-K. Compound 1 could be developed as a new anti-cancer agent since it increases the Bax/Bcl-2 ratio to overcome the drug resistance.
BIS-DIAZENIUMDIOLATE COMPOUNDS AS ANTI-CANCER AGENTS
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Paragraph 0040; 0041; 0048, (2019/04/25)
A series of double-component, bis O2-aryl diazeniumdiolate derivatives are provided, of which each molecule can release up to four nitric oxide molecules. These compounds show cytotoxic activities to cancer cells, such as human leukemia, breast cancer and lung cancer. Among them, the compound 3 showed the highest specific activity against human leukemia cells.