New Deoxycholic Acid Derived Tyrosyl-DNA Phosphodiesterase 1 Inhibitors Also Inhibit Tyrosyl-DNA Phosphodiesterase 2 was written by Salomatina, Oksana V.;Dyrkheeva, Nadezhda S.;Popadyuk, Irina I.;Zakharenko, Alexandra L.;Ilina, Ekaterina S.;Komarova, Nina I.;Reynisson, Johannes;Salakhutdinov, Nariman F.;Lavrik, Olga I.;Volcho, Konstantin P.. And the article was included in Molecules in 2022.Product Details of 422560-40-5 The following contents are mentioned in the article:
A series of deoxycholic acid (DCA) amides containing benzyl ether groups on the steroid core were tested against the tyrosyl-DNA phosphodiesterase 1 (TDP1) and 2 (TDP2) enzymes. In addition, 1,2,4- and 1,3,4-oxadiazole derivatives were synthesized to study the linker influence between a para-bromophenyl moiety and the steroid scaffold. The DCA derivatives demonstrated promising inhibitory activity against TDP1 with IC50 in the submicromolar range. Furthermore, the amides and the 1,3,4-oxadiazole derivatives inhibited the TDP2 enzyme but at substantially higher concentration Tryptamide I and para-bromoanilide II derivatives containing benzyloxy substituent at the C-3 position and non-substituted hydroxy group at C-12 on the DCA scaffold inhibited both TDP1 and TDP2 as well as enhanced the cytotoxicity of topotecan in non-toxic concentration in vitro. According to mol. modeling, ligand I was anchored into the catalytic pocket of TDP1 by one hydrogen bond to the backbone of Gly458 as well as by π-π stacking between the indolyl rings of the ligand and Tyr590, resulting in excellent activity. Therefore it could be concluded that these derivatives contributed to the development of specific TDP1 and TDP2 inhibitors for adjuvant therapy against cancer in combination with topoisomerase poisons. This study involved multiple reactions and reactants, such as 2-(4-Bromophenyl)-N-hydroxyacetimidamide (cas: 422560-40-5Product Details of 422560-40-5).
2-(4-Bromophenyl)-N-hydroxyacetimidamide (cas: 422560-40-5) belongs to organobromine compounds. Bromo compounds are employed in a variety of metal-catalyzed coupling reactions. They are also ideal candidates for the synthesis of Grignard reagents that have wide-applicability in organic synthesis. In the pharmaceutical industry organo bromine derivatives are used as sedatives, vasodilators, antiseptic agents, and anticancer agents.Product Details of 422560-40-5
Referemce:
Bromide – Wikipedia,
bromide – Wiktionary