6,9-Bis[(aminoalkyl)amino]benzo[g]isoquinoline-5,10-diones. A Novel Class of Chromophore-Modified Antitumor Anthracene-9,10-diones: Synthesis and Antitumor Evaluations

Abstract

Synthetic procedures have been developed which lead to the 2-aza congeners 3 and several related N-oxides 4. The analogues 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.

Synthesis and In Vitro Cytotoxicity Evaluation of Novel Naphthindolizinedione Derivatives

“…The difference in bioactivity of N,N-dimethylaminoethyl as far as the N,N-diethylaminoethyl chain is concerned, is similar to the result of modified anthracene-9,10-diones, where the structural features of the side chain and the antileukaemic activity were correlated. In particular, this study exhibited that both the steric variation on the distal nitrogen and the basic characteristics of the amino group significantly affected the antitumour bioactivity [15]. As far as the difference in the substituents on the quinone moiety are concerned, the data for compound 12b are quite similar to those obtained for 11b, indicating that the additional presence of the hydroxyl groups does not play an important role.…”

The role of pixantrone in the treatment of non-Hodgkin’s lymphoma

“…Pixantrone was first formulated as one of a series of 21 azaanalogues of the anthracene-9,10-dione class of antitumour agents [25]. Antitumor activity screening was performed and exhibited good in vivo activity against P388 leukaemia in mice [25].…”

Synthesis, Characterization, and Antimicrobial Evaluation of Quinoline-Oxadiazole–Based Azetidinone Derivatives

“…[4] Regarding structural and chemical modifications of this system, one of the most interesting modifications has been the introduction of hetero atoms (N, S) into different positions of the chromophore through incorporation of one or more of five-or six-membered heterocyclic rings to the basic quinoline system. [5][6][7] These bioisosteres would clearly differ from their carbocyclic counterparts in their interaction with DNA and enzymes, as well as in their reduction potential.…”