Synthesis and structure–activity relationship studies of 4,11-diaminonaphtho[2,3-f]indole-5,10-diones

Naphtho[2,3-f]indole-5,10-dione aminoalkyl derivatives: A new class of topoisomerase I inhibitors

“…The mechanism of inhibition differs from that realized with the use of catalytic blocker camptothecine and is presumably associated with direct reaction of naphthoindole diones with DNA. It is important that the range of concentrations in which compounds 4-11 inhibited topo I, coincided with the interval of concentrations causing death of K562 human leukemia cells [6][7][8]. In addition, compounds 7 and 11 (the most potent inhibitors of topo I) proved to be highly toxic for 60 human tumor cell strains (according to screening data of National Institute of Cancer Research, USA).…”

“…Naphtho[2,3-f]indole-5,10-dione 4,11-di(aminoethylamino) derivatives are structural analogs of ametantrone and mitoxantrone (antitumor drugs) and are synthesized by replacement of the methoxy group with ethylene diamine derivatives (compounds 4-7; Fig. 3, a) [7]. Other chemicals, 4,11-dihydroxynaphtho[2,3-f)-indole-5,10-dione 3-aminomethyl derivatives, were obtained in several stages including Mannich's reaction and methoxy group demethylation (compounds 8-11; Fig.…”

“…1) containing active (aminoalkyl) groups in various positions are characterized by high antiproliferative activity. Some compounds cause death of drugresistant tumor cells [6][7][8]. Presumably, naphtho[2,3-f]indole-5,10-dione derivatives bind to DNA and impair its structure.…”

Synthesis of New Cytotoxic Aminoanthraquinone Derivatives via Nucleophilic Substitution Reactions

“…It has also been reported that amino-substituted anthraquinones show significantly increased antiproliferative activities against human/mammalian cancer cell lines [21,22] and are known to have potential antitumor activity, but are less toxic to normal cells and display low cardiotoxicity [23,24,25,26]. A study on 4-( N -cyclohexylamino)-emodin implied that it can discriminate well between hepatoma cells and primary hepatocytes and it retained the capacity to reverse the multi-drug-resistance phenotype [27].…”

Synthesis and properties of a novel brominated oligomycin A derivative

“…4 Bromo-oligomycin A (2) was low cytotoxic against HCT116 human colon cancer cell line and K562 human leukemia cell line (IC 50 16.0 ± 2.2 and 9.0 ± 1.4 mM, respectively), whereas the parental compound (1) was significantly more potent (IC 50 3.3±1.0 and 3.0±1.0 mM, respectively) as determined by MTT-test after a 72 h incubation. 5 Furthermore, (2) was weakly active against Streptomyces fradiae strain that is extremely sensitive to (1) (250 nM per disk and 0.001 nM per disk, respectively).…”