14446-60-7Relevant articles and documents
Antimalarial acridines: Synthesis, in vitro activity against P. falciparum and interaction with hematin
Guetzoyan, Lucie,Yu, Xiao-Min,Ramiandrasoa, Florence,Pethe, Stephanie,Rogier, Christophe,Pradines, Bruno,Cresteil, Thierry,Perree-Fauvet, Martine,Mahy, Jean-Pierre
, p. 8032 - 8039 (2009)
A series of acridine derivatives were synthesised and their in vitro antimalarial activity was evaluated against one chloroquine-susceptible strain (3D7) and three chloroquine-resistant strains (W2, Bre1 and FCR3) of Plasmodium falciparum. Structure-activity relationship showed that two positives charges as well as 6-chloro and 2-methoxy substituents on the acridine ring were required to exert a good antimalarial activity. The best compounds possessing these features inhibited the growth of the chloroquine-susceptible strain with an IC50 ≤ 0.07 μM, close to that of chloroquine itself, and that of the three chloroquine-resistant strains better than chloroquine with IC50 ≤ 0.3 μM. These acridine derivatives inhibited the formation of β-hematin, suggesting that, like CQ, they act on the haem crystallization process. Finally, in vitro cytotoxicity was also evaluated upon human KB cells, which showed that one of them 9-(6-ammonioethylamino)-6-chloro-2-methoxyacridinium dichloride 1 displayed a promising antimalarial activity in vitro with a quite good selectivity index versus mammalian cell on the CQ-susceptible strain and promising selectivity on other strains.
Efficient photocleavage of DNA by cationic porphyrin-acridine hybrids with the effective length of diamino alkyl linkage
Ishikawa,Yamashita,Uno
, p. 287 - 293 (2001)
Positively charged porphyrins bearing an acridine with various lengths of diamino alkyl linkage, 5-[4-[(6-chloro-2- methoxy-9-acridyl)aminoalkylaminocarbonyl]phenyl]-10,15,20-tris (4-N-methylpyridiniumyl)porphine triiodide, alkyl=ethyl, butyl, hexyl, of o
Tricyclic "oxadiazaphosphorine oxide" guanosines a new strategy to functionalize guanosine at the exocyclic amino group
Guo, Yunkui
, p. 6651 - 6654 (1995)
A simple procedure is described for the preparation of modified guanosines via an oxidiazaphosphorine oxide guanosine derivative. This nucleoside has been successfully used in the synthesis of guanosine containing -(CH2)2OH, -(CH2)6NH2, -NHNH2 "handles", or a tethered acridine moiety at the 2-position.
Synthesis and in vitro biological evaluation of aminoacridines and artemisinin-acridine hybrids
Joubert, Juan P.,Smit, Frans J.,Du Plessis, Lissinda,Smith, Peter J.,N'da, David D.
, p. 16 - 27 (2014)
During this study, 9-aminoacridine and artemisinin-acridine hybrid compounds were synthesized and the in vitro for antimalarial activity against both the chloroquine sensitive but also gametocytocidal strain (NF54), and chloroquine resistant (Dd2) strains of Plasmodium falciparum was determined. In vitro cytotoxicity against CHO cells, apoptosis of HepG2 and SH-SY5Y as well as anticancer activity against HeLa cell lines were assessed. The hybrids were synthesized, using a microwave-assisted radiation method by covalently linking artemisinin and acridine pharmacophores by means of a liable, aminoethyl ether linker. The synthesized compounds were found active against both the Plasmodium strains and displayed superior selective toxicity towards the parasitic cells. Hybrid 7, however, containing ethylenediamine linker, proved the most active of all of the synthesized compounds. It had seven-fold higher antigametocytocidal activity compared to chloroquine and was also found to be seven-fold more potent than chloroquine against the Dd2 strain, with highly selective action towards the parasitic cells. This hybrid also showed favourable anti-cancer activity against the HeLa cells, three- and eight-fold higher than those of chloroquine and melphalan, respectively. This hybrid may therefore stand as drug candidate for further investigation in the search for new and effective drugs against malaria and cervical cancer.
Antitumour and antimalarial activity of artemisinin-acridine hybrids
Jones, Michael,Mercer, Amy E.,Stocks, Paul A.,La Pensée, Louise J.I.,Cosstick, Rick,Park, B. Kevin,Kennedy, Miriam E.,Piantanida, Ivo,Ward, Stephen A.,Davies, Jill,Bray, Patrick G.,Rawe, Sarah L.,Baird, Jonathan,Charidza, Tafadzwa,Janneh, Omar,O'Neill, Paul M.
, p. 2033 - 2037 (2009)
Artemisinin-acridine hybrids were prepared and evaluated for their in vitro activity against tumour cell lines and a chloroquine sensitive strain of Plasmodium falciparum. They showed a 2-4-fold increase in activity against HL60, MDA-MB-231 and MCF-7 cells in comparison with dihydroartemisinin (DHA) and moderate antimalarial activity. Strong evidence that the compounds induce apoptosis in HL60 cells was obtained by flow cytometry, which indicated accumulation of cells in the G1 phase of the cell cycle.
Solvent- and chromatography-free amination of π-deficient nitrogen heterocycles under microwave irradiation. A fast, efficient and green route to 9-aminoacridines, 4-aminoquinolines and 4-aminoquinazolines and its application to the synthesis of the drugs amsacrine and bistacrine
Staderini, Matteo,Cabezas, Nieves,Bolognesi, Maria Laura,Menéndez, J. Carlos
, p. 1024 - 1030 (2013/02/23)
Focused microwave irradiation of equimolecular mixtures of 9-chloroacridines, 4-chloroquinolines and 4-chloroquinazolines with amines in the presence of 2 equiv of phenol allows the general, fast and high-yielding synthesis of aminated heterocycles, with a very broad scope in terms of amine structure (aromatic, linear primary aliphatic, α-branched primary aliphatic, secondary aliphatic and diamines). Workup consisted of a simple washing with water and purification could be achieved by crystallization, avoiding the use of organic solvents in extraction and chromatographic purification steps. This protocol provides a solution to the long-standing synthetic problem of achieving a practical and efficient method for the amination of π-deficient nitrogen heterocycles for medicinal chemistry applications.
