Abstract:
:Alzheimer's disease (AD) is the most common type of dementia and related to the degeneration of hippocampal cholinergic neurons, which dramatically affects cognitive ability. Acetylcholinesterase (AChE) inhibitors are employed as drugs for AD therapy. Three series of sulfonylhydrazone compounds were designed, and their ability to inhibit AChE was evaluated. Fifteen compounds were synthesized and twelve of them had IC50 values of 0.64-51.09 μM. The preliminary structure-activity relationships indicated that the methylcatechol moiety and arylsulfonyl substituents generated better compounds than both the benzodioxole and alkylsulfonyl chains. Molecular dynamics studies of compound 6d showed that the interaction with the peripheral binding site of AChE was similar to donepezil, which may explain its low IC50 (0.64 μM). Furthermore, the drug-likeness of 6d suggests that the compound may have appropriate oral absorption and brain penetration. Compound 6d also presented antiradical activity and was not cytotoxic to LL24 cells, suggesting that this compound might be considered safe. Our findings indicate that arylsulfonylhydrazones may be a promising scaffold for the design of new drug candidates for the treatment of AD.
journal_name
Arch Pharm (Weinheim)journal_title
Archiv der Pharmazieauthors
Fernandes TB,Cunha MR,Sakata RP,Candido TM,Baby AR,Tavares MT,Barbosa EG,Almeida WP,Parise-Filho Rdoi
10.1002/ardp.201700163subject
Has Abstractpub_date
2017-11-01 00:00:00issue
11eissn
0365-6233issn
1521-4184journal_volume
350pub_type
杂志文章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::A new series of 1,4-disubstituted phthalazinylpiperazine derivatives 7a-f, 12a-f and 20a-f were designed and synthesized in order to develop potent and selective antitumor agents. The target compounds were screened for their cytotoxic activities against A549, HT-29 and MDA-MB-231 cancer cell lines in vitro. Among them...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/ardp.201100250
更新日期:2012-04-01 00:00:00
abstract::Mono-Mannich bases, 1-aryl-3-phenethylamino-1-propanone hydrochlorides, 1a, 2a, 3a, 4a, 5a, 6a, 7a, 8a, 9a, and semi-cyclic mono-Mannich bases, 3-aroyl-4-aryl-1-phenethyl-4-piperidinols, 1b, 2b, 3b, 4b, 5b, 6b, 7b, 8b, 9b, were synthesized by a non-classical Mannich reaction. The aryl part was: C(6)H(5 )for 1a, 1b; 4-...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/ardp.200900136
更新日期:2010-05-01 00:00:00
abstract::Rapamycin, a potent antifungal antibiotic, was approved as immunosuppressant, and lately its derivatives have been developed into mTOR targeting anticancer drugs. Structure modification was performed at the C-42 position of rapamycin, and a novel series of rapamycin triazole hybrids (4a-d, 5a-e, 8a-e, and 9a-e) was fa...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/ardp.201500457
更新日期:2016-06-01 00:00:00
abstract::Fourteen new 1-[(N, N-disubstituted thiocarbamoylthio)acetyl]-3-(2-thienyl)-5-aryl-2-pyrazoline derivatives (7a-n) were synthesised by reacting 1-(chloroacetyl)-3-(2-thienyl)-5-aryl-2-pyrazolines (5a-g) and appropriate sodium salts of N, N-disubstituted dithiocarbamoic acids (6a, b). The structures of the synthesised ...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/ardp.200400935
更新日期:2005-03-01 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::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::Based upon molecular modeling, the pharmacophore of potential inhibitors of p38 MAPK (mitogen-activated protein kinases) is discussed and the predictive binding affinities are calculated. Syntheses of original diarylimidazo[2,1-a]phthalazines obtained by Suzuki coupling are described. ...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/1521-4184(200201)335:1<7::aid-ardp7>3.0.co
更新日期:2002-01-01 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::Synthesis of 2-chloro-1,1-dimethylethyl and 2-chloro-2,2-dimethylethyl analogues of ifosfamide was performed via aziridine intermediate. In vitro metabolic activation showed that both compounds are metabolised at a rate similar to the parent drug. However, their anticancer activity against L1210 leukaemia in mice was ...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/1521-4184(200109)334:8/9<291::aid-ardp291>
更新日期:2001-09-01 00:00:00
abstract::Three ketomethylene pseudodideptide analogues [(S)Lys psi(COCH2)(R and S)Phe (14 or 15 and 15 or 14) and (S)Lys psi(COCH2)(xi Trp (19)] of natural arphamenine A [(S)Arg psi(COCH2(R,S)Phe (1)] were easily prepared by a route involving two successive main reactions: a malonic ester alkylation with Z-protected lysine iod...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/ardp.19923250103
更新日期:1992-01-01 00:00:00
abstract::The synthesis of new bischromone derivatives (4a-c and 5a-c) as potential anticancer drugs is described. The difference in the reactivity between 4-oxo-4H-chromene-3-carboxylic acid 2 (or its methyl ester 3) and 4-oxo-4H-chromene-3-carbonyl chloride 1 with three different polyamines: 3,3'-diamino-N-methyldipropylamine...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/ardp.201200220
更新日期:2013-01-01 00:00:00
abstract::An overview of the rhodopsin crystal structure provides a structural basis for understanding the structures and functions of other G-protein coupled receptors (GPCRs). All of the structural details observed to date for rhodopsin will not necessarily carry over to other GPCRs, but major features such as the arrangement...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章,评审
doi:10.1002/ardp.200400995
更新日期:2005-06-01 00:00:00
abstract::(2S,3R)-3,7-Diamino-2-hydroxy-heptanoyl-Leu-Pro-OH [(2S,3R)-DAHHA-Leu-Pro-OH, 4], analogue of the N-terminal tripeptide of probestin, has been synthesized, and tested as inhibitor of AP-B, Leu-AP, AP-M, and enkephalin-degrading APs, and as analgesic. In order to establish structure-activity relationships the dipeptide...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/ardp.19923250812
更新日期:1992-08-01 00:00:00
abstract::N-Methoxyquinolinium salts 3 are prepared as potential cardiotonic agents by alkylation of the corresponding N-oxides 2 synthesized by two different methods. 1. Oxidation of some quinoline derivatives 1 using 30% H2O2 or 3-chloroperbenzoic acid. 2. Nitration of the quinoline-N-oxides 2a, 2c, and 2m. Preparation of 2h ...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/ardp.19933260410
更新日期:1993-04-01 00:00:00
abstract::A series of cis-restricted 4,5-diaryl-3-aminopyrazole derivatives were synthesized and tested for their cytotoxic activity in vitro against five human cancer cell lines (K562, ECA-109, A549, SMMC-7721, and PC-3). Compounds 5a, 5b, 5d, and 6b showed potent cytotoxicity against all tested cell lines. Primary mechanism r...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/ardp.201000069
更新日期:2011-05-01 00:00:00
abstract::2-Acetyl-(6-picolyl)-4N-substituted thiosemicarbazones and their copper(II) complexes were shown to be potent antineoplastic and cytotoxic agents against murine and human cultured cells. Numerous derivatives were as active against solid tumor growth as clinically useful agents. The agents inhibited L1210 DNA and RNA s...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/(sici)1521-4184(199804)331:4<121::aid-ardp
更新日期:1998-04-01 00:00:00
abstract::New series of perimidine derivatives and fused perimidines were derived from the reaction of ketene aminals 1 and 2 with diazotized anilines or hydrazonoyl chlorides. In addition, 8,10-disubstituted-[1,2,4]triazolo[4,3-a]perimidines (20a-m) were prepared through the reaction of perimidine-2-thione (15) with hydrazonoy...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/ardp.201200486
更新日期:2013-05-01 00:00:00
abstract::The preparation and detailed composition of an oil newly extracted from pure soy germ (not less than 96 % hypocotyle) are presented. Experiments in vivo showed that soybean-germ oil (SGO) possesses a remarkable protective activity against UVB-induced skin inflammation, exceeding that of tocopherol acetate by a factor ...
journal_title:Archiv der Pharmazie
pub_type: 临床试验,杂志文章
doi:10.1002/ardp.200500159
更新日期:2005-12-01 00:00:00
abstract::A range of novel pyridine-2,4,6-tricarbohydrazide thiourea compounds (4a-i) were synthesized in good to excellent yields (63-92%). The enzyme inhibitory potentials of these compounds were investigated against α- and β-glucosidases because these enzymes play a crucial role in treating type-2 diabetes mellitus (T2DM). A...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/ardp.201700236
更新日期:2018-01-01 00:00:00
abstract::In an attempt to find a new class of antibacterial agents, we have synthesized thirty new coumarin (2H-benzopyran-2-one) analogues. These derivatives include substituted azetidin-2-ones (beta-lactam) 3a-f, pyrrolidin-2-ones 4a-f, 2H-1,3,4-oxadiazoles 5a-f, and thiazolidin-4-ones 6a-f attached to 4-phenyl-2H-benzopyran...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/ardp.200700266
更新日期:2008-11-01 00:00:00
abstract::3-Ethyl 5-methyl 1,4-dihydro-2-[(2-hydroxyethoxy) methyl]-6-methyl-4-(2,3-dichlorophenyl)-3,5-pyridinedicarboxylate (13), a bioisostere of amlodipine, was prepared by the reaction of ethyl 4-(2-hydroxyethoxy)acetoacetate (11) with methyl 2-(2,3-dichlorobenzylidene)acetoacetate (12) and NH4OAc. Compound 13 was elaborat...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/(sici)1521-4184(199910)332:10<363::aid-ard
更新日期:1999-10-01 00:00:00
abstract::[4-(Adamantane-1-carboxamido)-3-oxo-1-thia-4-azaspiro[4.4]nonan-2-yl]acetic acid (4a) and [4-(adamantane-1-carboxamido)-8-nonsubstituted/substituted-3-oxo-1-thia-4-azas-piro[4.5]decane-2-yl]acetic acid (4b-g) derivatives were synthesized; their structures were verified by elemental analysis, infrared spectroscopy, 1 H...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/ardp.202000256
更新日期:2021-01-06 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::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::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::Numerous novel N,N-disubstituted 5-alkyliden- or 5-aralkyliden-3-aminorhodanines 2 have been prepared by condensation of carbonyl compounds with 1. The effectiveness of some derivatives in an "akanthose test" with hairless mice was shown. ...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/ardp.19933260609
更新日期:1993-06-01 00:00:00
abstract::The pyrrolidino enaminones, with the carboxylic acid chain fixed at the nitrogen, inhibit cyclooxygenase more potently or selectively than 5-lipoxygenase. According to the structure-activity relationships discussed the potency depends significantly on the chain length of the carboxylic acid, the substitution pattern o...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/ardp.19973300307
更新日期:1997-03-01 00:00:00
abstract::Structural feature analysis of chlorogenic acid derivatives made up of varying lengths of alkyl groups as α-glucosidases inhibitors were performed by QSAR techniques. The statistically significant models derived from the study were validated by leave one out, Y-randomization and test set methods. The predictive capaci...
journal_title:Archiv der Pharmazie
pub_type: 杂志文章
doi:10.1002/ardp.201100047
更新日期:2012-04-01 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