28971-67-7Relevant articles and documents
Structure-Activity Relationship Study of Dexrazoxane Analogues Reveals ICRF-193 as the Most Potent Bisdioxopiperazine against Anthracycline Toxicity to Cardiomyocytes Due to Its Strong Topoisomerase IIβ Interactions
Jirkovská, Anna,Karabanovich, Galina,Kube?, Jan,Skalická, Veronika,Melnikova, Iuliia,Korábe?ny, Jan,Ku?era, Tomá?,Jirkovsky, Eduard,Nováková, Lucie,Bavlovi? Piská?ková, Hana,?koda, Josef,?těrba, Martin,Austin, Caroline A.,?im?nek, Tomá?,Roh, Jaroslav
, p. 3997 - 4019 (2021/05/04)
Cardioprotective activity of dexrazoxane (ICRF-187), the only clinically approved drug against anthracycline-induced cardiotoxicity, has traditionally been attributed to its iron-chelating metabolite. However, recent experimental evidence suggested that the inhibition and/or depletion of topoisomerase IIβ (TOP2B) by dexrazoxane could be cardioprotective. Hence, we evaluated a series of dexrazoxane analogues and found that their cardioprotective activity strongly correlated with their interaction with TOP2B in cardiomyocytes, but was independent of their iron chelation ability. Very tight structure-activity relationships were demonstrated on stereoisomeric forms of 4,4′-(butane-2,3-diyl)bis(piperazine-2,6-dione). In contrast to its rac-form 12, meso-derivative 11 (ICRF-193) showed a favorable binding mode to topoisomerase II in silico, inhibited and depleted TOP2B in cardiomyocytes more efficiently than dexrazoxane, and showed the highest cardioprotective efficiency. Importantly, the observed ICRF-193 cardioprotection did not interfere with the antiproliferative activity of anthracycline. Hence, this study identifies ICRF-193 as the new lead compound in the development of efficient cardioprotective agents.
Stereoselective Grignard reactions to α-amino nitrones. Synthesis of optically active α-aminohydroxylamines and 1,2-diamines
Merino, Pedro,Lanaspa, Ana,Merchan, Francisco L.,Tejero, Tomas
, p. 2381 - 2401 (2007/10/03)
α-Aminohydroxylamines are formed stereoselectively from the nucleophilic addition of phenylmagnesium bromide to α-amino nitrones. In contrast, the addition of methylmagnesium bromide occurs in a stereorandom fashion. Nevertheless it is possible to achieve a complete syn selectivity by diprotecting the α-amino group in the starting nitrone. Hydrogenation of the obtained α-amino hydroxylamines followed by deprotection of the tert-butoxycarbonyl group affords optically active 1,2-diamines.
