Abstract:
:The histone deacetylase (HDAC) enzyme plays an important role in gene transcription. Inhibitors of histone deacetylases induce cell differentiation and suppress cell proliferation in tumor cells. Hydroxamates with rigid linker have displayed better inhibition profiles than those with linear and flexible aliphatic linkers. We have designed and synthesized several potential histone deacetylase inhibitors with a piperazine moiety in the linker region to test the effect of reduced linker flexibility. Inhibitors were evaluated for their inhibitory action on human HDAC3/NCoR2 and HDAC8. N-Hydroxycarboxamide derivatives (compounds 4a-d) were found to be better than N-hydroxyacetamide derivatives (compounds 6a-d) against HDAC8. Amongst the synthesized compounds, 4a (HDAC8, IC50: 3.15 microM) with no substitution in the aryl cap was the most active and promising lead for further investigations.
journal_name
Arch Pharm (Weinheim)journal_title
Archiv der Pharmazieauthors
Chakrabarty S,Jasmine,Bhadaliya C,Sinha BN,Mahesh A,Bai H,Blond SY,Jayaprakash Vdoi
10.1002/ardp.200900117subject
Has Abstractpub_date
2010-03-01 00:00:00pages
167-72issue
3eissn
0365-6233issn
1521-4184journal_volume
343pub_type
杂志文章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...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/ardp.201900170
更新日期:2019-12-01 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::Enantiomerically pure 1, 2-diamino-1-(4-fluorophenyl)propanes were synthesized by stereospecific and stereoselective procedures by use of the (1R, 2S)- and (1S, 2R)-2-amino-1-(4-fluorophenyl)propanols (12a) as intermediates. The enantiomeric purity was determined by (1)H NMR spectroscopy after conversion of the propan...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/1521-4184(200205)335:5<229::AID-ARDP229>3.
更新日期:2002-05-01 00:00:00
abstract::6-Amino-5-imino-pyrazolo[4',3':5,6]pyrano[2,3-d]pyrimidine derivative 4 and pyrazolo-[4',3':5,6]pyrano[2,3-d]pyrimidin-5-ylhydrazine derivative 5 were prepared starting from 6-amino-3-methyl-4-(p-nitrophenyl)-2,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile 1. The synthesis and structure characterization of 9,11-dihydr...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/ardp.200700007
更新日期:2007-07-01 00:00:00
abstract::A series of oximes deriving from 5-arylidene-pyrrolidine-2,3,4-triones and pyridine-2,3,4-triones has been prepared. The presence of the tautomeric nitrosoenol was proven in solutions of alpha-ketooxime 7a. The binding affinity of the new oximes toward the N-methyl-D-aspartate (glycine site) receptor has been measured...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/(sici)1521-4184(19999)332:9<309::aid-ardp3
更新日期:1999-09-01 00:00:00
abstract::The active form of vitamin D3 , calcitriol, is a potent antiproliferative compound. However, when effective antitumor doses of calcitriol are used, hypercalcemic effects are observed, thus blocking its therapeutic application. To overcome this problem, structural analogues have been designed with the aim of retaining ...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/ardp.201800315
更新日期:2019-05-01 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::Cancer can invade or spread to almost all parts of the body. The increasing morbidity and high mortality of cancer create a great demand for the development of novel anticancer drugs. Coumarin derivatives are ubiquitous in nature and can readily interact with diverse enzymes and receptors in cancer cells via weak bond...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章,评审
doi:10.1002/ardp.202000025
更新日期:2020-08-01 00:00:00
abstract::The activity of 72 1,4-dihydropyridines as calcium channel antagonists was examined. The simplified molecular input-line entry system (SMILES) was used as representation of the molecular structure of the calcium channel antagonists. Quantitative structure-activity relationships (QSARs) were developed using CORAL softw...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/ardp.201200373
更新日期:2013-02-01 00:00:00
abstract::Increases in the intracellular levels of glutathione (GSH) in cancer cells have been implicated in the development of acquired resistance to platinum antitumor agents. On the other hand, little information is available on the relationships between intracellular GSH levels in non-treated cancer cells and their response...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/ardp.200400620
更新日期:2004-12-01 00:00:00
abstract::This paper reports the synthesis of the new compound 1-[2-acetoxy-3-(4-phenyl-1-piperazinyl)propyl]pyrrolidin-2-one (Ac-MG-1). Preliminary pharmacological assessment revealed that Ac-MG-1 possesses anti-arrhythmic activity and a local anesthetic effect. The crystal structure of Ac-MG-1 was determined by X-ray diffract...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/ardp.19953280613
更新日期:1995-06-01 00:00:00
abstract::Three novel series of quinoline derivatives have been prepared by cyclization of the intermediate 3-(1,3-dioxolan-2-yl)-2-substituted thiocarbamoyl-hydrazinoquinolines with different alpha-halocarbonyl compounds. These series are: 3-(1,3-dioxolan-2-yl)-2-(3-substituted-4-phenylthiazolin-2-y lidene) hydrazinoquinolines...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/ardp.19903230414
更新日期:1990-04-01 00:00:00
abstract::The 5-desoxy analogue of BW245C, imidazolidin-2-one 3, has been synthesized by reduction of the N-benzyl hydantoin derivative 6. Compound 3 was found to be approximately equipotent with BW245C as an inhibitor of platelet aggregation and this result indicates that the 5-keto group of BW245C is not essential for platele...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/ardp.2503240802
更新日期:1991-08-01 00:00:00
abstract::Several 2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)-1H-benzimidazole-5-carboxamidine analogues were synthesized for their antibacterial and antifungal activities against S. aureus, Methicillin-resistant S. aureus (MRSA), C. albicans, and C. krusei. MIC values of the targeted compounds 43-58 are comparabl...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/ardp.200500168
更新日期:2006-02-01 00:00:00
abstract::The synthesis and biological evaluation of ethyl 8-oxo-5,6,7,8-tetrahydro-thiazolo[3,2-a][1,3]diazepin-3-carboxylate (HIE-124, 4), as a member of a new generation of ultra-short acting hypnotics is described. HIE-124 4 exhibited potent in-vivo activity with a very rapid onset of action and a shorter duration of action...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/ardp.200700132
更新日期:2008-02-01 00:00:00
abstract::Synthesis of some new derivatives of 2-aryl-4-oxo-1-(4-quinazolyl)quinazolines is described. Methyl N-(4-quinazolyl)anthranilate was allowed to react with phenyl iso(thio)cyanate to give 3-phenyl-1-(4-quinazolyl)-1, 2, 3, 4-tetrahydro-2, 4-dioxo- and 4-oxo-2-thioxoquinazolines (3a and 3b respectively) Alternatively, a...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/ardp.200290009
更新日期:2002-01-01 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::The oncoprotein cytotoxic associated gene A (CagA) of Helicobacter pylori plays a pivotal role in the development of gastric cancer, so it has been an important target for anti-H. pylori drugs. Conventional drugs are currently being implemented against H. pylori. The inhibitory role of plant metabolites like curcumin ...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/ardp.201400438
更新日期:2015-08-01 00:00:00
abstract::A novel dimer of 2-(4-pyridylmethyl)-1-indanone (2) was obtained while carrying out aldol condensation of 1-indanone with pyridine-4-carboxaldehyde in potassium hydroxide. The structure of dimer 3 has been established using various spectral techniques and was screened for its ability to inhibit the cytochrome P(450) e...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/ardp.200400853
更新日期:2004-07-01 00:00:00
abstract::A series of 1-¿omega-(4-aryl-1-piperazinyl)alkyl]indolin-2(1H)-one derivatives 2-14 was synthesized in order to obtain ligands with a dual 5-HT1A/5-HT2A activity. The majority of those compounds (2-5, 7, 10-13) exhibited a high 5-HT1A (Ki = 2-44 nM) and/or 5-HT2A affinity (Ki = 51 and 39 for 5 and 7, respectively). In...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/(sici)1521-4184(199810)331:10<325::aid-ard
更新日期:1998-10-01 00:00:00
abstract::The precise definition of the structural requirements for effective topoisomerase II poisoning by drug molecules is still an elusive issue. In the attempt to better define a pharmacophoric pattern, we prepared several conjugates combining the chemical features of two well-known topoisomerase II poisons, amsacrine and ...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/ardp.201400111
更新日期:2014-10-01 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::A series of 3,4-bis-chalcone-N-arylpyrazoles 3a-k was prepared from diacetyl pyrazoles 2a-e. The reaction of 2d and 2e with hydrazine hydrate gave pyrazolo[3,4-d]pyridazine derivatives 4a-b. Furthermore, the reaction of 2a-e with thiosemicarbazide afforded pyrazolo[3,4-d]pyridazine thiocyanate salts 5a-e. The synthesi...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/ardp.201300193
更新日期:2013-09-01 00:00:00
abstract::Phosphono-analogues of glutathione containing the O = P(OR)2 moiety in place of the cysteinyl residue CH2SH 1a-1d were prepared by solution phase peptide synthesis. Benzyl, benzyloxy-carbonyl, and tert-butyl protecting groups were used to mask the individual amino acid functional groups. The formation of peptide bonds...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/ardp.19963291106
更新日期:1996-11-01 00:00:00
abstract::New, non-imidazole histamine H3 receptor antagonists were prepared and in vitro tested as H3 receptor antagonists measured as the electrically evoked contraction of the guinea-pig jejunum. The 2-(1-piperidinyl)- and 2-(1-pyrrolidinyl)benzothiazoles show no or very poor activity; 2-[1-(4-amino)piperidinyl]- and 2-(1,2-...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/(sici)1521-4184(199911)332:11<389::aid-ard
更新日期:1999-11-01 00:00:00
abstract::Schiff base transition metal complexes are an important class of compounds with great potential for therapeutic interventions. However, data on antileukemic and antilymphoma effects of these complexes are limited. The activity of N,N'-bis(salicylidene)-1,2-phenylenediamine (salophene, 1), its iron(II/III) and manganes...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/ardp.201000237
更新日期:2011-04-01 00:00:00
abstract::Reaction of K2PtCl4 with the substituted 2-aminomethylpyridines 9, 14, and 22 affords the corresponding dichloroplatinum(II) complexes 3-5. Compounds 3 and 22 show remarkable relative binding affinities for the estrogen receptor. Towards the hormone-independent P388-tumor of the CD2F1-mouse the platinum(II) complexes ...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:
更新日期:1991-10-01 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
abstract::Poly(vinyl alcohol) was crosslinked with ethylene glycol diglycidyl ether to obtain hydrogel-forming polymers. The polymers were also substituted with oleoyl chloride, providing hydrogels with weak solubility. These new polymeric materials were evaluated for the formulation of sustained drug delivery systems. Vancomyc...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/1521-4184(200203)335:2/3<89::AID-ARDP89>3.
更新日期:2002-03-01 00:00:00
abstract::Derivatives of the recently described potent neuroprotective 7-O-cinnamoylsilibinin ester were prepared: its hemisuccinate to improve water solubility and the dehydrosilibinin ester that was shown to form in assay media to investigate its role in overall neuroprotective effects. 7-O-Cinnamoyl-2,3-dehydrosilibinin is l...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/ardp.201800206
更新日期:2018-11-01 00:00:00