Abstract:
:Two series of amino-1,4-benzoquinones (AQ1-18) based on the structural analogs of plastoquinones were synthesized and the structure-activity relationship against chronic myelogenous leukemia activity was examined. All of the synthesized compounds were tested for their cytotoxic effects on different leukemic cell lines. Of interest, AQ15 exhibited a better selectivity than the reference drug imatinib on cancer cells. Owing to this, AQ15 was selected for a further apoptosis/necrosis evaluation where AQ15-treated K562 cells demonstrated similar apoptotic effects like imatinib-treated cells at their IC50 values. The inhibitory effects of AQ15 and the other three compounds with various activities against eight tyrosine kinases, including ABL1, were investigated. AQ15 showed weak activity against ABL1, and a correlation was observed between the anti-K562 and anti-ABL1 activities. The binding mode of AQ15 into the ATP binding pocket of ABL1 kinase was predicted in silico, showing the formation of some key interactions. In addition, AQ15 was shown to suppress the downstream signaling of BCR-ABL in K562 cells. Finally, AQ15 obviously cleaved DNA in the presence of an iron(II) complex system, indicating that this can be the major mechanism of its antiproliferative action, whereas the mild inhibition of ABL kinase is just in-part mechanism of its overall outstanding cellular activity.
journal_name
Arch Pharm (Weinheim)journal_title
Archiv der Pharmazieauthors
Ciftci HI,Bayrak N,Yıldırım H,Yıldız M,Radwan MO,Otsuka M,Fujita M,Tuyun AFdoi
10.1002/ardp.201900170subject
Has Abstractpub_date
2019-12-01 00:00:00pages
e1900170issue
12eissn
0365-6233issn
1521-4184journal_volume
352pub_type
杂志文章abstract::A series of 4β-[(4-substituted)-1,2,3-triazol-1-yl]podophyllotoxin congeners were synthesized by employing click chemistry and further evaluated for their antitumor activity by MTT assay. Among them, six congeners (10, 11, 12, 13, 22, and 24) exhibited approximately 100-fold more potent inhibitory activity against fou...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/ardp.201100438
更新日期:2012-12-01 00:00:00
abstract::To identify new agents for the treatment of American cutaneous leishmaniasis, a series of eight 1,4-bis(substituted benzalhydrazino)phthalazines was evaluated against Leishmania braziliensis and Leishmania mexicana parasites. These compounds represent a disubstituted version of the 1-chloro-4-(monoaryl/heteroarylhydra...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/ardp.201800299
更新日期:2019-06-01 00:00:00
abstract::A 3D pharmacophore model predicting anticonvulsant activity was obtained for a series of 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline derivatives recently disclosed as a new class of noncompetitive AMPA receptor antagonists. The training set included 17 compounds with varying potency against audiogenic seizures in DBA...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/ardp.200600022
更新日期:2006-07-01 00:00:00
abstract::10 is a beta-carboline analogue of the neuroleptic flutroline2a,b) with significant lower affinity at the dopamine D2 binding site. Various synthetic routes to 10 and the solid state structure of 8 are described, structure activity relations, in particular the importance of the "S-shape" and the rigid dopamine conform...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/ardp.19933261206
更新日期:1993-12-01 00:00:00
abstract::A new class of acetamidomethylsulfonyl bis heterocycles-oxazolyl-1,3,4-oxadiazoles, -thiazolyl-1,3,4-oxadiazoles, and -imidazolyl-1,3,4-oxadiazoles were synthesized from the synthetic intermediates, methyl 2-((4-aryloxazol-2-ylcarbamoyl)methylsulfonyl)acetate, methyl 2-((4-arylthiazol-2-ylcarbamoyl)methylsulfonyl)acet...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/ardp.201300115
更新日期:2013-07-01 00:00:00
abstract::Starting from the commercially available 6-methyl-2-pyridylamine (1) the pyrido[3,2-e][1,4]diazepine 14a was synthesized in 12 steps with 7% total yield. 14a, the N-methyl derivative 14b, the thiolactam 15a, the amidine 16, and the 1,2,4-triazole 17 were tested for anti-HIV-1-activity. None of the compounds tested pos...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/ardp.19953280308
更新日期:1995-03-01 00:00:00
abstract::A novel series of N-(2-(piperazin-1-yl)phenyl)aryl carboxamide derivatives were simply synthesized by Ugi-multicomponent reaction as β-secretase (BACE1) inhibitors. The BACE1 inhibitory activity of the synthesized compounds was examined using a Forester resonance energy transfer (FRET)-based assay. Among the tested co...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/ardp.201400322
更新日期:2015-05-01 00:00:00
abstract::Various aryl 1-pyrryl sulfones were synthesized and tested as inhibitors of HIV-1. 2-Nitrophenyl-2-ethoxycarbonyl-1-pyrryl sulfone, the most active among test derivatives, was selected as lead compound of the aryl pyrryl sulfone series. The in vitro anti-HIV-1 activity and cytotoxicity of 41 compounds is reported. Som...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/ardp.19953280304
更新日期:1995-03-01 00:00:00
abstract::Although a large number of pharmaceutical therapies are available to treat cardiovascular diseases like heart failure, in many medical conditions treatment is still not optimal and, therefore, the need for innovative, safe and efficacious drugs is still very high in this indication. Biomarkers are an important tool in...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章,评审
doi:10.1002/ardp.201600055
更新日期:2016-06-01 00:00:00
abstract::A series of 5-alkyl-5-phenylbarbituric acid analogues were shown to be potent hypolipidemic agents in rats and mice at 20 mg/kg/day. This dose is lower than that required for hypolipidemic activity for clofibrate and nicotinic acid derivatives in rodents and man. These new derivatives reduced both serum cholesterol an...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/ardp.19903230905
更新日期:1990-09-01 00:00:00
abstract::Nine novel acyl thioureas were synthesized. Their identities and purities were confirmed by LC-MS spectra; each structure was elucidated by elemental analysis, IR, 1 Н and 13 C NMR spectra. Applying an in vitro screening of their antifungal potential, three substances (3, 5, and 6) could be selected as showing high ac...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/ardp.201800275
更新日期:2019-02-01 00:00:00
abstract::With the purpose of expanding the structural variety of chemical compounds available as pharmacological tools for the treatment of Alzheimer's disease, we synthesized and evaluated a novel series of indole-benzoxazinones (Family I) and benzoxazine-arylpiperazine derivatives (Family II) for potential human acetylcholin...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/ardp.201800024
更新日期:2018-05-01 00:00:00
abstract::In accordance with the significant impetus of the discovery of potent vascular endothelial growth factor receptor 2 (VEGFR-2) inhibitors, herein, we report the design, synthesis, and anticancer evaluation of 12 new N-substituted-4-phenylphthalazin-1-amine derivatives against HepG2, HCT-116, and MCF-7 cells as VEGFR-2 ...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/ardp.202000219
更新日期:2020-11-16 00:00:00
abstract::A series of novel N-(4,5-dihydroimidazol-2-yl)-1,3-dihydrobenzimidazole derivatives 2a-d, 3a-d and 4a-p were prepared and their structure was determined by IR and NMR spectroscopic data as well as X-ray analysis of carbonitrile 2a. The compounds were studied as potential inhibitors of the human blood platelet aggregat...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/(sici)1521-4184(199807)331:7/8<241::aid-ar
更新日期:1998-07-01 00:00:00
abstract::Both 2-nitrooxymethyl-4-phenyl- (2) and 4-nitrooxymethylphenyl-1,4-dihydropyridines (3) represent new combinations of two different vasodilating structures. 2 could not be isolated due to its spontaneous lactonization. Derivatives of 3 were obtained via Hantzsch synthesis using nitrooxymethylated benzaldehydes. The in...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/ardp.19973300804
更新日期:1997-08-01 00:00:00
abstract::We report in this work the synthesis, cytotoxicity, and antimicrobial activity of ([1,2,4]triazolo[1,5-c]quinazolin-2-ylthio)carboxylic acid amides 4-7 in connection with our previous research in the preparation of triazoloquinazoline derivatives. Due to simplicity, general availability of starting materials, and high...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/ardp.200900077
更新日期:2009-11-01 00:00:00
abstract::Starting from L-aspartic acid the preparation of 8-aminopyrido[1,2-a]indole derivatives as benzo-fused analogs of the dopamine autoreceptor agonist 1 is reported. The key step of the synthesis is the Tf2O induced cyclization of the 1,2-amino alcohol 6. Receptor binding studies indicated selective affinity for the D-2 ...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/ardp.19953280712
更新日期:1995-07-01 00:00:00
abstract::A series of 7, 7'-alkylene-bridged dimers(7a-e) of the benz [d]indolo[3, 2-f]azecine derivative LE300 was synthesized. Affinity and functional activity at dopamine D(1) and D(2) receptors were estimated by radioligand binding and a functional Ca(2+) assay. All the new bivalent ligands showed significant binding affini...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/1521-4184(200211)335:8<367::AID-ARDP367>3.
更新日期:2002-08-01 00:00:00
abstract::Albumin binding for the enantiomers of four closely related N-methyl-5-phenyl-5-alkyl-barbiturates 1-4 was investigated for three different mammalian species by means of equilibrium dialysis. Lipid solubility (n-heptane/phosphate buffer distribution coefficient) increased stepwise by a factor of 56 from 1 to 4. Bovine...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/ardp.19963290805
更新日期:1996-08-01 00:00:00
abstract::Isatin and azole moieties, which have the ability to form various noncovalent interactions with different therapeutic targets, are common pharmacophores in drug development. Isatin and azole derivatives possess promising in vitro and in vivo anticancer activity, and many of them, such as semaxanib, sunitinib, and carb...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章,评审
doi:10.1002/ardp.201900272
更新日期:2020-01-01 00:00:00
abstract::Gypsogenin (1) was obtained by acidic hydrolysis from its saponin. While the parent compound 1 acted as a selective inhibitor for butyrylcholinesterase (from equus) possessing a moderate mixed-type inhibition of the enzyme, Ki values as low as 2.67 ± 0.59 μM were determined for (3β,4α) 3-O-acetyl-olean-12-ene-23,28-di...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/ardp.201400103
更新日期:2014-10-01 00:00:00
abstract::Structural studies of hydroxy-aluminum phosphates with antacid application are performed. The antacid properties of the products depend on their chemical composition and way of preparation. Scanning electron microscope, X-ray- and IR-spectroscopy have evidenced the formation of a one-phase product. The IR-spectra indi...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/ardp.19903230802
更新日期:1990-08-01 00:00:00
abstract::Solid-state Nuclear Magnetic Resonance (NMR) provides a general method to study molecular structure and dynamics in a non-crystalline and insoluble environment. We discuss the latest methodological progress to construct 3D molecular structures from solid-state NMR data obtained under magic-angle-spinning conditions. A...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章,评审
doi:10.1002/ardp.200400991
更新日期:2005-06-01 00:00:00
abstract::A series of 6-chloro-3-(4-alkylphenyl)-4-thioxo-2H-1,3-benzoxazine-2(3H)-ones, 7-chloro-3-(4-alkylphenyl)-4-thioxo-2H-1,3-benzoxazine-2(3H)-ones, 6-bromo-3-(4-alkylphenyl)-4-thioxo-2H-1,3-benzoxazine-2(3H)-ones, 6,8-dibromo-3-(4-alkylphenyl)-4-thioxo-2H-1,3-benzoxazine-2(3H)-ones, 6-chloro-3-(4-alkylphenyl)-2H-1,3-ben...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/ardp.200800004
更新日期:2008-12-01 00:00:00
abstract::The biotransformation of the positively inotropically active compound N-methyl-N-(2-hydroxy-3-phenoxy-propyl)-11-(2-aminoethyl)-6,11- dihydrodibenz[b,e]-oxepine, neutral fumarate, (Doxaminol, racemic mixture of diastereomeres) in dogs is examined. The metabolits M1-M7 were isolated and their chemical structures identi...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/ardp.19903230503
更新日期:1990-05-01 00:00:00
abstract::Herein, we report the synthesis of novel tetrahydro-β-carbolines that induce cell death via the autophagic pathway. Five of the new compounds induced cell death in a panel of patient-derived human metastatic melanoma cells. The autophagic pathway was confirmed using LC3 autophagosome markers; the involvement of ATG7 a...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/ardp.201300437
更新日期:2014-06-01 00:00:00
abstract::Antibiotic-resistant bacteria continue to play an important role in human health and disease. Inventive strategies are necessary to develop new therapeutic leads to challenge drug-resistance problems. From this perception, new quinoline hybrids bearing bioactive pharmacophores were synthesized. The newly synthesized c...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/ardp.201900086
更新日期:2019-10-01 00:00:00
abstract::Several chloro- and iodo-lignanolides have been obtained by direct halogenation of aromatic rings from yatein and 4'-O-demethylyatein. They were assayed as antineoplastics, in order to check the influence in the activity of substitution in both aromatic rings. Although these compounds show a modest antineoplastic acti...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/ardp.19953280903
更新日期:1995-09-01 00:00:00
abstract::Polyketide-derived macrolactones like zearalenone (1), zearalane (2) or curvularin (3) display a wide range of interesting pharmacological activities. Here, we present a short and efficient approach towards this class of natural products by a combination of the Sonogashira and Mitsunobu reactions. The resulting lacton...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/ardp.200500132
更新日期:2005-12-01 00:00:00
abstract::The complex of lanthanum (III) was synthesized reacting the respective inorganic salt with 5-aminoorotic acid in amounts equal to the metal:ligand molar ratio of 1:3. The complex was prepared by adding an aqueous solution of lanthanum (III) nitrate to an aqueous solution of the ligand, subsequently raising the pH of t...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/ardp.200600077
更新日期:2006-11-01 00:00:00