185540-17-4Relevant articles and documents
10-(4-Phenylpiperazine-1-carbonyl)acridin-9(10H)-ones and related compounds: Synthesis, antiproliferative activity and inhibition of tubulin polymerization
Waltemate, Jana,Ivanov, Igor,Ghasemi, Jahan B.,Aghaee, Elham,Daniliuc, Constantin Gabriel,Müller, Klaus,Prinz, Helge
supporting information, (2020/11/27)
As part of our continuing search for potent inhibitors of tubulin polymerization, two novel series of 42 10-(4-phenylpiperazine-1-carbonyl)acridin-9(10H)-ones and N-benzoylated acridones were synthesized on the basis of a retrosynthetic approach. All newly synthesized compounds were tested for antiproliferative activity and interaction with tubulin. Several analogs potently inhibited tumor cell growth. Among the compounds tested, 10-(4-(3-methoxyphenyl)piperazine-1-carbonyl)acridin-9(10H)-one (17c) exhibited excellent growth inhibitory effects on 93 tumor cell lines, with an average GI50 value of 5.4 nM. We were able to show that the strong cytotoxic effects are caused by disruption of tubulin polymerization, as supported by the EBI (N,N'-Ethylenebis(iodoacetamide)) assay and the fact that the most potent inhibitors of cancer cell growth turned out to be the most efficacious tubulin polymerization inhibitors. Potencies were nearly comparable or superior to those of the antimitotic reference compounds. Closely related to this, the most active analogs inhibited cell cycling at the G2/M phase at concentrations down to 30 nM and induced apoptosis in K562 leukemia cells. We believe that our work not only proves the excellent suitability of the acridone scaffold for the design of potent tubulin polymerization inhibitors but also enables synthetic access to further potentially interesting N-acylated acridones.
Photoreaction of 2-halo-N-pyridinylbenzamide: Intramolecular cyclization mechanism of phenyl radical assisted with n-complexation of chlorine radical
Park,Jung,Kim,Kim,Song,Kim
, p. 2197 - 2206 (2007/10/03)
The photochemical behavior of 2-halo-N-pyridinylbenzamide (1-4 in Chart 1) was studied. The photoreaction of 2-chloro-N-pyridinylbenzamides 1a, 2a, 3a, and 4 afforded photocyclized products, benzo[c]naphthyridinones (6-9 and 16), in high yield, whereas the bromo analogues 1b, 2b, and 3b produced extensively photoreduced products, N-pyridinylbenzamides (1c, 10, and 11), with minor photocyclized product. Since the photocyclization reaction of 2-chloro-N-pyridinylbenzamide is retarded by the presence of oxygen and sensitized by the presence of a triplet sensitizer, acetone or acetophenone, a triplet state of the chloro analogue is involved in the reaction. Since several radical intermediates, particularly n-complexes of chlorine radical, are identified in the laser flash photolysis of 2-chloro-N-pyridinylbenzamide, an intramolecular cyclization mechanism of phenyl radical assisted with n-complexation of chlorine radical for the cyclization reaction is proposed: the triplet state (78 kcal/mol) of the chloro analogue (1a), which is populated by the excitation of 1a undergoes a homolytic cleavage of the C-Cl bond to give phenyl and chlorine radicals; while chlorine radical holds the neighbor pyridinyl ring with its n-complexation, the intramolecular arylation of the phenyl radical with the pyridinyl ring proceeds to produce a conjugated 2,3-dihydropyridinyl radical and then the conjugated radical aromatizes to afford a cyclized product, benzo[c]naphthyridinone by ejecting a hydrogen. The photoreduction product can be formed by hydrogen atom abstraction of the phenyl a radical from the environment.
