144511-12-6Relevant articles and documents
New anthracenedione derivatives with improved biological activity by virtue of stable drug-DNA adduct formation
Mansour, Oula C.,Evison, Benny J.,Sleebs, Brad E.,Watson, Keith G.,Nudelman, Abraham,Rephaeli, Ada,Buck, Damian P.,Collins, J. Grant,Bilardi, Rebecca A.,Phillips, Don R.,Cutts, Suzanne M.
experimental part, p. 6851 - 6866 (2010/12/25)
Mitoxantrone is an anticancer agent that acts as a topoisomerase II poison, however, it can also be activated by formaldehyde to form DNA adducts. Pixantrone, a 2-aza-anthracenedione with terminal primary amino groups in its side chains, forms formaldehyde-mediated adducts with DNA more efficiently than mitoxantrone. Molecular modeling studies indicated that extension of the "linker" region of anthracenedione side arms would allow the terminal primary amino greater flexibility and thus access to the guanine residues on the opposite DNA strand. New derivatives based on the pixantrone and mitoxantrone backbones were synthesized, and these incorporated primary amino groups as well as extended side chains. The stability of DNA adducts increased with increasing side chain length of the derivatives. A mitoxantrone derivative bearing extended side chains (7) formed the most stable adducts with ～100-fold enhanced stability compared to mitoxantrone. This finding is of great interest because long-lived drug-DNA adducts are expected to perturb DNA-dependent functions at all stages of the cell cycle.
6,9-bis[(2-aminoethyl)amino]benzo[g]isoquinoline-5,10-dione and its dimaleate salt
-
, (2008/06/13)
In the search for novel heteroanalogs of anthracendiones, 6,9-bis[(2-aminoethyl)amino]benzo[g]isoquinoline-5,10-dione dimaleate salt (BBR 2778), was selected as the most promising compound. New methods of synthesis produce the compound in purity greater than 99%.
6,9-Bisbenzoisoquinoline-5,10-diones. A Novel Class of Chromophore-Modified Antitumor Anthracene-9,10-diones: Synthesis and Antitumor Evaluations
Krapcho, A. Paul,Petry, Mary E.,Getahun, Zelleka,Landi, John J.,Stallman, John,et al.
, p. 828 - 837 (2007/10/02)
Synthetic procedures have been developed which lead to the 2-aza congeners 3 and several related N-oxides 4.The analoques 3 exhibited a wide range of in vitro cytotoxicity against L1210 leukemia, the human colon adenocarcinoma cell line LoVo, and the doxorubicin resistant LoVo/DX cell line.Selected analogues of 3 showed significant P388 antileukemic activity in mice with 3c exhibiting high activity.This activity was also retained in the related N-oxide 4a.These heterocyclic bioisosteric models are representative of the first anthracene-9,10-diones which display antileukemic activity comparable to mitoxantrone.
