99009-51-5Relevant articles and documents
Utilizing genome-wide mrna profiling to identify the cytotoxic chemotherapeutic mechanism of triazoloacridone C-1305 as direct microtubule stabilization
Baginski, Maciej,Bartoszewska, Sylwia,Bartoszewski, Rafal,Biernatowska, Agnieszka,Collawn, James F.,Crossman, David K.,Dudkowska, Magdalena,Janiszewska, Dorota,Króliczewski, Jaros?aw,Krzymiński, Karol,Markuszewski, Michal,Ochocka, Renata J.,Romanowska, Anna,Sikora, Ewa,Sikorski, Aleksander F.,Wysocka, Ma?gorzata
, (2020)
Rational drug design and in vitro pharmacology profiling constitute the gold standard in drug development pipelines. Problems arise, however, because this process is often difficult due to limited information regarding the complete identification of a molecule’s biological activities. The increasing affordability of genome-wide next-generation technologies now provides an excellent opportunity to understand a compound’s diverse effects on gene regulation. Here, we used an unbiased approach in lung and colon cancer cell lines to identify the early transcriptomic signatures of C-1305 cytotoxicity that highlight the novel pathways responsible for its biological activity. Our results demonstrate that C-1305 promotes direct microtubule stabilization as a part of its mechanism of action that leads to apoptosis. Furthermore, we show that C-1305 promotes G2 cell cycle arrest by modulating gene expression. The results indicate that C-1305 is the first microtubule stabilizing agent that also is a topoisomerase II inhibitor. This study provides a novel approach and methodology for delineating the antitumor mechanisms of other putative anticancer drug candidates.
Novel inhibitors of NRH:Quinone oxidoreductase 2 (NQO2): Crystal structures, biochemical activity, and intracellular effects of imidazoacridin-6-ones
Dunstan, Mark S.,Barnes, John,Humphries, Matthew,Whitehead, Roger C.,Bryce, Richard A.,Leys, David,Stratford, Ian J.,Nolan, Karen A.
, p. 6597 - 6611 (2011/12/01)
Imidazoacridin-6-ones are shown to be potent nanomolar inhibitors of the enzyme NQO2. By use of computational molecular modeling, a reliable QSAR was established, relating inhibitory potency with calculated binding affinity. Further, crystal structures of
2-(Aminoalkyl)-5-nitropyrazoloacridines, a New Class of Anticancer Agents
Capps, David B.,Dunbar, James,Kesten, Suzanne R.,Shillis, Joan,Werbel, Leslie M.,et al.
, p. 4770 - 4778 (2007/10/02)
2-(Aminoalkyl)-5-nitropyrazoloacridines were prepared from substituted anilines via the 1-chloro-4-nitroacridones followed by condensation with hydrazines.Impressive activity was demonstrated for the 9-hydroxy, 9-alkoxy, and 9-acyloxy analogs in vitro on a L1210 leukemia line and in vivo against the P388 leukemia.Advanced studies led to the selection of 3bbb for clinical trial.
