Novel Deazaflavin Analogues Potently Inhibited Tyrosyl DNA Phosphodiesterase 2 (TDP2) and Strongly Sensitized Cancer Cells toward Treatment with Topoisomerase II (TOP2) Poison Etoposide was written by Kankanala, Jayakanth;Ribeiro, Carlos J. A.;Kiselev, Evgeny;Ravji, Azhar;Williams, Jessica;Xie, Jiashu;Aihara, Hideki;Pommier, Yves;Wang, Zhengqiang. And the article was included in Journal of Medicinal Chemistry in 2019.COA of Formula: C8H7BrO2 This article mentions the following:
Topoisomerase II (TOP2) poisons as anticancer drugs work by trapping TOP2 cleavage complexes (TOP2cc) to generate DNA damage. Repair of such damage by tyrosyl DNA phosphodiesterase 2 (TDP2) could render cancer cells resistant to TOP2 poisons. Inhibiting TDP2, thus, represents an attractive mechanism-based chemosensitization approach. Currently known TDP2 inhibitors lack cellular potency and/or permeability. We report herein two novel subtypes of the deazaflavin TDP2 inhibitor core. By introducing an addnl. Ph ring to the N-10 Ph ring (subtype 11) or to the N-3 site of the deazaflavin scaffold (subtype 12), we have generated novel analogs with considerably improved biochem. potency and/or permeability. Importantly, many analogs of both subtypes, particularly compounds 11a, 11e, 12a, 12b, and 12h, exhibited much stronger cancer cell sensitizing effect than the best previous analog 4a toward the treatment with etoposide, suggesting that these analogs could serve as effective cellular probes. In the experiment, the researchers used many compounds, for example, 3-(Bromomethyl)benzoic acid (cas: 6515-58-8COA of Formula: C8H7BrO2).
3-(Bromomethyl)benzoic acid (cas: 6515-58-8) belongs to organobromine compounds. Most of the natural organobromine compounds are produced by marine organisms, and several brominated metabolites with antibacterial, antitumor, antiviral, and antifungal activity have been isolated from seaweed, sponges, corals, molluscs, and others. Many of the alkyl bromine derivatives are excellent alkylating agents since bromides are good leaving groups. Tribromides, like tetrabutylammonium tribromide, are used as a solid source of bromine. N-bromosuccimide (NBS) is used for the selective bromination of allylic bonds.COA of Formula: C8H7BrO2
Referemce:
Bromide – Wikipedia,
bromide – Wiktionary