Hu, De-Xuan published the artcileSynthesis of Methoxy-, Methylenedioxy-, Hydroxy-, and Halo-Substituted Benzophenanthridinone Derivatives as DNA Topoisomerase IB (TOP1) and Tyrosyl-DNA Phosphodiesterase 1 (TDP1) Inhibitors and Their Biological Activity for Drug-Resistant Cancer, Quality Control of 74317-85-4, the main research area is benzophenanthridinone preparation TOP1 TDP1 enzyme inhibitor antitumor SAR.
Herein, the synthesis of benzophenanthridinone derivatives I [R = 1-MeO, 2-Br, 8-OH, etc], II [R1 = R2 = 2,3-OCH2O, 8,9-Meo, 8,9-F], III [R3 = 8-F, 8-Br, 9-MeO; R4 = R5 = 2,3-OCH2O, 2,3-MeO, etc] as TOP1 and TDP1 inhibitors was reported. Seven compounds III [R3 = 8-F, 8-NO2, 8-MeO, 9-Cl, 7,8-OH, 8,9-F; R4 = R5 = 2,3-OCH2O] showed a robust TOP1 inhibitory activity (+++ or ++++), and four compounds I [R = 12-MeO] and III [R3 = 7,8-OH, 8-MeO, 8,9-MeO; R4 = R5 = 2,3-OCH2O, 8,9-MeO] showed a TDP1 inhibition (half-maximal inhibitory concentration values of 15 or 19μM). Also the dual TOP1 and TDP1 inhibitor III [R = 2,3-OCH2O, 7,8-OH] induces both cellular TOP1cc, TDP1cc formation and DNA damage was showed ,resulting in cancer cell apoptosis at a sub-micromolar concentration In addition, III [R = 2,3-OCH2O, 7,8-OH] showed an enhanced activity in drug-resistant MCF-7/TDP1 cancer cells and was synergistic with topotecan in both MCF-7 and MCF-7/TDP1 cells.
Journal of Medicinal Chemistry published new progress about Antitumor agents. 74317-85-4 belongs to class bromides-buliding-blocks, name is 2-Bromo-4-methoxybenzoic acid, and the molecular formula is C8H7BrO3, Quality Control of 74317-85-4.
Referemce:
Bromide – Wikipedia,
bromide – Wiktionary