当前位置： SCI文献检索 > BIOORGANIC CHEMISTRY期刊下所有文献 > Tacrine-hydroxamate derivatives as multitarget-directed ligands for the treatment of Alzheimer's disease: Design, synthesis, and biological evaluation.

Tacrine-hydroxamate derivatives as multitarget-directed ligands for the treatment of Alzheimer's disease: Design, synthesis, and biological evaluation.

Abstract：

:In order to develop multitarget-directed ligands as potential treatments for Alzheimer's disease, twenty-eight new tacrine-hydroxamate derivatives were designed, synthesized, and biologically evaluated. As expected, most of the compounds exhibited inhibitory activities against cholinesterases (ChEs) and histone deacetylase (HDACs). Among the tested compounds, A10 showed not only potent and selective inhibition on AChE at sub-nanomolar potency (AChEIC50 = 0.12 nM, BChEIC50 = 361.52 nM) but also potent inhibition on HDAC (IC50 = 0.23 nM). Moreover, A10 exhibited inhibitory activity on Aβ1-42 self-aggregation as well as disaggregation activity on pre-formed Aβ fibrils. Furthermore, A10 exhibited antioxidant activity and metal chelating properties. Further mechanistic studies demonstrated that A10 is a pan-inhibitor of HDACs and a mixed-type inhibitor for AChE. It shown that A10 is a BBB penetrant by online prediction. Taken together, the results indicate that A10 can serve as a lead compound to develop promising candidate analogs as AD therapeutics.

journal_name

Bioorg Chem

journal_title

Bioorganic chemistry

authors

Xu A,He F,Zhang X,Li X,Ran Y,Wei C,James Chou C,Zhang R,Wu J

doi

10.1016/j.bioorg.2020.103721

subject

Has Abstract

pub_date

2020-05-01 00:00:00

pages

103721

eissn

0045-2068

issn

1090-2120

pii

S0045-2068(19)32224-2

journal_volume

98

pub_type

杂志文章

相关文献

BIOORGANIC CHEMISTRY文献大全
  • Discovery of a novel cathepsin inhibitor with dual autophagy-inducing and metastasis-inhibiting effects on breast cancer cells.

    abstract：:Drug resistance and cancer cells metastasis have been the leading causes of chemotherapy failure and cancer-associated death in breast cancer patients. In present, various active molecules either exhibiting novel mechanism of action such as inducing autophagy or inhibiting metastasis have been developed to address the...

    journal_title：Bioorganic chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bioorg.2018.11.025

    authors： Yuan L,Liu J,He W,Bao Y,Sheng L,Zou C,Hu B,Ge W,Liu Y,Wang J,Lin B,Li Y,Ma E

    更新日期：2019-03-01 00:00:00

  • Discovery of imidazopyridine derivatives as novel c-Met kinase inhibitors: Synthesis, SAR study, and biological activity.

    abstract：:Receptor tyrosine kinase c-Met acts as an alternative angiogenic pathway in the process and contents of cancers. A series of imidazopyridine derivatives were designed and synthesized according to the established docking studies as possible c-Met inhibitors. Most of these imidazopyridine derivatives displayed nanomolar...

    journal_title：Bioorganic chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bioorg.2016.12.002

    authors： Yang Y,Zhang Y,Yang L,Zhao L,Si L,Zhang H,Liu Q,Zhou J

    更新日期：2017-02-01 00:00:00

  • Synthesis and biological evaluation of benzofuran-based 3,4,5-trimethoxybenzamide derivatives as novel tubulin polymerization inhibitors.

    abstract：:A new series of derivatives characterized by the presence of the 3,4,5-trimethoxylbenzamide substituted benzofurans were synthesized and evaluated for antiproliferative activity against four cancer cell lines and one normal human cell line. Among them, derivative 6g with greatest cytotoxicity significantly inhibited t...

    journal_title：Bioorganic chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bioorg.2020.104076

    authors： Li Q,Jian XE,Chen ZR,Chen L,Huo XS,Li ZH,You WW,Rao JJ,Zhao PL

    更新日期：2020-09-01 00:00:00

  • Synthesis, evaluation and molecular docking studies of amino acid derived N-glycoconjugates as antibacterial agents.

    abstract：:Six amino acid derived N-glycoconjugates of d-glucose were synthesized, characterized and tested for antibacterial activity against G(+)ve (Bacillus cereus) as well as G(-)ve (Escherichia coli and Klebsiella pneumoniae) bacterial strains. All the tested compounds exhibited moderate to good antibacterial activity again...

    journal_title：Bioorganic chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bioorg.2015.10.002

    authors： Baig N,Singh RP,Chander S,Jha PN,Murugesan S,Sah AK

    更新日期：2015-12-01 00:00:00

  • Design, synthesis and biological evaluation of methylenehydrazine-1-carboxamide derivatives with (5-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)-1H-indole scaffold: Novel potential CDK9 inhibitors.

    abstract：:In continuation of our previous work on the investigation of CDK9 inhibitors bearing indole moiety for the discovery of novel anticancer agents, novel methylenehydrazine-1-carboxamide derivatives with (5-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)-1H-indole scaffold were designed, synthesized, and evaluated for the CDK9 i...

    journal_title：Bioorganic chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bioorg.2020.104064

    authors： Hu H,Wu J,Ao M,Zhou X,Li B,Cui Z,Wu T,Wang L,Xue Y,Wu Z,Fang M

    更新日期：2020-09-01 00:00:00

  • Sulfonamides incorporating piperazine bioisosteres as potent human carbonic anhydrase I, II, IV and IX inhibitors.

    abstract：:Starting from the molecular simplification of (R) 4-(3,4-dibenzylpiperazine-1-carbonyl)benzenesulfonamide 9a, a compound endowed with selectivity for human Carbonic Anhydrase (hCA) IV, a series of piperazines and 4-aminopiperidines carrying a 4-sulfamoylbenzamide moiety as Zn-binding group have been designed and teste...

    journal_title：Bioorganic chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bioorg.2019.103130

    authors： Chiaramonte N,Bua S,Angeli A,Ferraroni M,Picchioni I,Bartolucci G,Braconi L,Dei S,Teodori E,Supuran CT,Romanelli MN

    更新日期：2019-10-01 00:00:00

  • Design, synthesis and anti-diabetic activity of triazolotriazine derivatives as dipeptidyl peptidase-4 (DPP-4) inhibitors.

    abstract：:Type 2 diabetes mellitus (T2DM) is one of the major global metabolic disorders characterized by insulin resistance and chronic hyperglycemia. Inhibition of the enzyme, dipeptidyl peptidase-4 (DPP-4) has been proved as successful and safe therapy for the treatment of T2DM since last decade. In order to design novel DPP...

    journal_title：Bioorganic chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bioorg.2017.03.004

    authors： Patel BD,Bhadada SV,Ghate MD

    更新日期：2017-06-01 00:00:00

  • Activity and mechanism of action of insect oostatic peptides in flesh fly.

    abstract：:The relationship between structure and activity of insect oostatic decapeptide (Aed-TMOF) analogues in flesh fly was analyzed. The highest oostatic activity was exhibited by the pentapetide and tetrapeptide analogues, H-Tyr-Asp-Pro-Ala-Pro-OH and H-Tyr-Asp-Pro-Ala-OH, respectively. The tetrapeptide, either native or t...

    journal_title：Bioorganic chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bioorg.2004.05.003

    authors： Slaninová J,Bennettová B,Nazarov ES,Simek P,Holík J,Vlasáková V,Hlavácek J,Cerný B,Tykva R

    更新日期：2004-08-01 00:00:00

  • Eight new glycosides with hepatoprotective activity isolated from the aerial parts of Morinda parvifolia.

    abstract：:Eight new glycosides, morindaparvins P-W, were isolated from the butanol extract of the aerial parts of Morinda parvifolia. These new structures were elucidated by comprehensive spectroscopic analysis and by comparing the experimental and calculated electronic circular dichroism spectra. The butanol extract was observ...

    journal_title：Bioorganic chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bioorg.2018.11.055

    authors： Su X,Li L,Sun H,Zhang F,Li C,Li F,Wang H,Li B,Chen R,Kang J

    更新日期：2019-06-01 00:00:00

  • 3, 9-di-O-substituted coumestrols incorporating basic amine side chains act as novel apoptosis inducers with improved pharmacological selectivity.

    abstract：:There is much interest in the use of phytoestrogens such as coumestrol in breast cancer intervention due to their antiestrogenic activity and multiple modes of tumor cell death. However, the clear beneficial effects of naturally occurring estrogen mimetic coumestrol remain controversial due to experimental evidence th...

    journal_title：Bioorganic chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bioorg.2018.12.024

    authors： Luo G,Tang Z,Li X,Hou Q,Chen Y,Lao K,Xiang H

    更新日期：2019-04-01 00:00:00

  • ent-Pimarane diterpenoids from Siegesbeckia glabrescens with anti-inflammatory activity.

    abstract：:Nine new ent-pimarane-type diterpenoids, siegesbeckia A-I (1-9), together with four known analogues ent-3α,15,16,19-tetrahydroxypimar-8(14)-ene (10), 15,16-dihydroxypimar-8(14)-en-3-one (11), 14β,16-epoxy-7-pimarene-3α,15β-diol (12) and darutigenol (13), were obtained from the aerial parts of Siegesbeckia glabrescens ...

    journal_title：Bioorganic chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bioorg.2020.103854

    authors： Gao X,Rong Z,Long G,Hu G,Yan T,Li N,Jia J,Wang A

    更新日期：2020-06-01 00:00:00

  • Design, synthesis, and evaluations of the antiproliferative activity and aqueous solubility of novel carbazole sulfonamide derivatives as antitumor agents.

    abstract：:Optimization of IG-105 (1) on the carbazole ring provided five series of new carbazole sulfonamides derivatives, 7a-e, 8a-g, 9a-g, 10a-e, and 11a-g. All of the compounds were evaluated against HepG2, MCF-7, MIA PaCa-2, and Bel-7402 cells for antiproliferative activity. Each series of compounds was 2-5 times more activ...

    journal_title：Bioorganic chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bioorg.2020.103766

    authors： Sun L,Wang C,Hu X,Wu Y,Jiang Z,Li Z,Chen X,Hu L

    更新日期：2020-06-01 00:00:00

  • Structure-activity relationship studies of prostate-specific membrane antigen (PSMA) inhibitors derived from α-amino acid with (S)- or (R)-configuration at P1' region.

    abstract：:Prostate-specific membrane antigen (PSMA), a type II membrane glycoprotein, is considered an excellent target for the diagnosis or treatment of prostate cancer. We previously investigated the effect of β- and γ-amino acids with (S)- or (R)-configuration in the S1 pocket on the binding affinity for PSMA. However, compr...

    journal_title：Bioorganic chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bioorg.2020.104304

    authors： Kwon H,Lim H,Ha H,Choi D,Son SH,Nam H,Minn I,Byun Y

    更新日期：2020-11-01 00:00:00

  • Synthesis and DNase I inhibitory properties of some 5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidines.

    abstract：:A series of six novel and six known thieno[2,3-d]pyrimidin-4-amines 2-13 were synthesized, and further were used as a starting material for preparation of a small series of eight novel thieno[2,3-d]pyrimidin-4-phthalimides 14-21. Eight compounds, five amine and three phthalimide derivatives, inhibited bovine pancreati...

    journal_title：Bioorganic chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bioorg.2018.07.009

    authors： Ts Mavrova A,Dimov S,Yancheva D,Kolarević A,Ilić BS,Kocić G,Šmelcerović A

    更新日期：2018-10-01 00:00:00

  • Facile green bio-fabricated silver nanoparticles from Microchaete infer dose-dependent antioxidant and anti-proliferative activity to mediate cellular apoptosis.

    abstract：:With the rapid development of nanotechnology, much has been anticipated with silver nanoparticles (AgNPs) due to their extensive industrial and commercial applications. However, it has raised concerns over environmental safety and human health effects. In this study, AgNPs were bio-fabricated using aqueous extract of ...

    journal_title：Bioorganic chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bioorg.2020.104535

    authors： Husain S,Verma SK,Yasin D,Hemlata,A Rizvi MM,Fatma T

    更新日期：2020-12-11 00:00:00

  • Design, synthesis, anti-inflammatory antitumor activities, molecular modeling and molecular dynamics simulations of potential naprosyn® analogs as COX-1 and/or COX-2 inhibitors.

    abstract：:Inflammation is a fundamental physiological process that is essential for survival of human being but at the same time is one of the major causes of human morbidity and mortality. In the past decade, numerous advances have taken place in the understanding and development of novel anti-inflammatory drugs. Therefore, in...

    journal_title：Bioorganic chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bioorg.2017.11.002

    authors： El Sayed MT,El-Sharief MAMS,Zarie ES,Morsy NM,Elsheakh AR,Nayel M,Voronkov A,Berishvili V,Sabry NM,Hassan GS,Abdel-Aziz HA

    更新日期：2018-02-01 00:00:00

  • Heterocyclic periphery in the design of carbonic anhydrase inhibitors: 1,2,4-Oxadiazol-5-yl benzenesulfonamides as potent and selective inhibitors of cytosolic hCA II and membrane-bound hCA IX isoforms.

    abstract：:A series of novel aromatic primary sulfonamides decorated with diversely substituted 1,2,4-oxadiazole periphery groups has been prepared using a parallel chemistry approach. The compounds displayed a potent inhibition of cytosolic hCA II and membrane-bound hCA IX isoforms. Due to a different cellular localization of t...

    journal_title：Bioorganic chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bioorg.2017.10.005

    authors： Krasavin M,Shetnev A,Sharonova T,Baykov S,Tuccinardi T,Kalinin S,Angeli A,Supuran CT

    更新日期：2018-02-01 00:00:00

  • Compounds from the fruits of mangrove Sonneratia apetala: Isolation, molecular docking and antiaging effects using a Caenorhabditis elegans model.

    abstract：:The chemical investigation of the fruits of a mangrove Sonneratia apetala collected from the Beibu Gulf led to the isolation of four new compounds, sonneradons A-D (1-4), as well as 18 known compounds (5-22). The structures of the new compounds were elucidated based on extensive spectroscopic analysis, and the structu...

    journal_title：Bioorganic chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bioorg.2020.103813

    authors： Yi X,Jiang S,Qin M,Liu K,Cao P,Chen S,Deng J,Gao C

    更新日期：2020-06-01 00:00:00

  • 1-(4-Methane(amino)sulfonylphenyl)-3-(4-substituted-phenyl)-5-(4-trifluoromethylphenyl)-1H-2-pyrazolines/pyrazoles as potential anti-inflammatory agents.

    abstract：:2-Pyrazolins 14a-l and pyrazoles 15a-l were designed as celecoxib analogs for the evaluation of their in vitro COX-1/COX-2 inhibitory activity and the in vivo anti-inflammatory activity. Compounds 14i, 15a, 15d and 15f were the most COX-2 selective derivatives (S.I.=5.93, 6.08, 5.03 and 5.27 respectively) while the py...

    journal_title：Bioorganic chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bioorg.2015.09.002

    authors： Abdellatif KR,Elshemy HA,Azoz AA

    更新日期：2015-12-01 00:00:00

  • Chemoenzymatic synthesis of enantiomerically enriched diprophylline and xanthinol nicotinate.

    abstract：:A concise chemoenzymatic route toward enantiomerically enriched active pharmaceutical ingredients (API) - diprophylline and xanthinol nicotinate - is reported for the first time. The decisive step is an enantioselective lipase-mediated methanolysis of racemic chlorohydrin-synthon acetate, namely 1-chloro-3-(1,3-dimeth...

    journal_title：Bioorganic chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bioorg.2020.104448

    authors： Borowiecki P,Młynek M,Dranka M

    更新日期：2021-01-01 00:00:00

  • Quinoxalines as potent selective CRFRs ligands for monitoring and brain diagnostic.

    abstract：:The paper highlighted quinoxalines as potent ligands to corticotropin-releasing factor receptor types 1 and 2. The content includes design and structure-activity relationship of 50 model substances to CRFR1, CRFR2α and CRF2β, respectively. It is important to bear in mind, that our concept has based on challenging rese...

    journal_title：Bioorganic chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bioorg.2014.10.008

    authors： Ivanova B,Spiteller M

    更新日期：2015-02-01 00:00:00

  • Non-viral vectors for the mediation of RNAi.

    abstract：:Though the delivery of siRNA into cells, tissues or organs remains to be a big obstacle for its applications, recently siRNA therapeutics has developed rapidly and already there are clinical trials ongoing or planned. Some non-viral vectors have attracted much more attention and shown the great potential for combating...

    journal_title：Bioorganic chemistry

    pub_type： 杂志文章,评审

    doi：10.1016/j.bioorg.2011.07.005

    authors： Zhang S,Zhao Y,Zhi D,Zhang S

    更新日期：2012-02-01 00:00:00

  • Taxumarienes A-G, seven new α-glucosidase inhibitory taxane-diterpenoids from the leaves of Taxus mairei.

    abstract：:Seven new taxane diterpenoids taxumarienes A-G (1-7) were isolated from the leaves of Taxus mairei, along with seven known analogous (8-14). The structures of the new compounds were elucidated based on the analysis of NMR and MS spectroscopy. All isolates were evaluated for their α-glucosidase inhibitory activities. A...

    journal_title：Bioorganic chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bioorg.2019.103400

    authors： Chen K,Liu XQ,Wang WL,Luo JG,Kong LY

    更新日期：2020-01-01 00:00:00

  • Fusicoccane-derived diterpenoids with bridgehead double-bond-containing tricyclo[9.2.1.03,7]tetradecane ring systems from Alternaria brassicicola.

    abstract：:Fusicoccane-derived diterpenoids bearing a unique bridgehead double-bond-containing tricyclo[9.2.1.03,7]tetradecane (5-9-5 ring system) core skeleton represent a rarely reported class of rearranged terpenoids, which traced back to fusicoccanes with a classical dicyclopenta[a,d]cyclooctane (5-8-5 ring system) core skel...

    journal_title：Bioorganic chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bioorg.2020.103887

    authors： Li F,Pan L,Lin S,Zhang S,Li H,Yang B,Liu J,Wang J,Hu Z,Zhang Y

    更新日期：2020-07-01 00:00:00

  • Synthesis of dual-action parthenolide prodrugs as potent anticancer agents.

    abstract：:Cancer stem cells are responsible for the failure of a large number of cancer treatments and the re-emergence of cancer in patients. Parthenolide is a potent anticancer sesquiterpene lactone that is also able to kill cancer stem cells. The main problem with this compound is its poor solubility in water. To solve this ...

    journal_title：Bioorganic chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bioorg.2017.01.020

    authors： Taleghani A,Nasseri MA,Iranshahi M

    更新日期：2017-04-01 00:00:00

  • Design, synthesis and biological evaluation of novel β-pinene-based thiazole derivatives as potential anticancer agents via mitochondrial-mediated apoptosis pathway.

    abstract：:A series of novel β-pinene-based thiazole derivatives were synthesized and characterized by HRMS, 1H NMR, and 13C NMR analyses as potential antineoplastic agents. Derivatives were evaluated for their anticancer activities in vitro, and the data manifested that most target compounds showed potent anti-proliferative act...

    journal_title：Bioorganic chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bioorg.2018.12.010

    authors： Wang Y,Wu C,Zhang Q,Shan Y,Gu W,Wang S

    更新日期：2019-03-01 00:00:00

  • Quinazoline-4(3H)-one derivatives as novel and potent inhibitors of soluble epoxide hydrolase: Design, synthesis and biological evaluation.

    abstract：:Inhibition of soluble epoxide hydrolase (sEH) is considered as a promising target to reduce blood pressure, improve insulin sensitivity, and decrease inflammation. In this study, a series of some novel quinazoline-4(3H)-one derivatives (3a-t) with varying steric and electronic properties was designed, synthesized and ...

    journal_title：Bioorganic chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bioorg.2020.103736

    authors： Hejazi L,Rezaee E,Tabatabai SA

    更新日期：2020-06-01 00:00:00

  • Design, synthesis and photoinduced DNA cleavage studies of [1,2,4]-triazolo[4,3-a]quinoxalin-4(5H)-ones.

    abstract：:An expedient and eco-friendly synthesis of 1-aryl/heteroaryl-[1,2,4]-triazolo[4,3-a]quinoxalin-4(5H)-ones (4) has been accomplished via iodobenzene diacetate mediated oxidative intramolecular cyclization of 3-(2-(aryl/heteroarylidene)hydrazinyl)-quinoxalin-2(1H)-ones (3). Ten synthesized compounds 3 and 4 (10-40 μg) o...

    journal_title：Bioorganic chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bioorg.2019.102932

    authors： Sumran G,Aggarwal R,Mittal A,Aggarwal A,Gupta A

    更新日期：2019-07-01 00:00:00

  • Cytotoxicity of oleanolic and ursolic acid derivatives toward hepatocellular carcinoma and evaluation of NF-κB involvement.

    abstract：:Oleanolic and ursolic acids are two ubiquitous isomeric triterpene phytochemicals known for their anticancer activity. A set of derivatives of the two compounds with a modified oxidation state and lipophylicity at C-3 and C-28 positions, were prepared and tested as anticancer agents versus the lines HepG2, Hep3B and H...

    journal_title：Bioorganic chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bioorg.2019.103054

    authors： Fontana G,Bruno M,Notarbartolo M,Labbozzetta M,Poma P,Spinella A,Rosselli S

    更新日期：2019-09-01 00:00:00

  • Pesimquinolones I-S, eleven new quinolone alkaloids produced by Penicillium simplicissimum and their inhibitory activity on NO production.

    abstract：:Eleven undescribed quinolone alkaloids, pesimquinolones I-S (1-4 and 6-12), as well as eleven known congeners (5 and 13-22), were isolated from the solid culture broth of the fungus Penicillium simplicissimum. Their chemical structures with absolute configurations were established by a combination of NMR spectroscopy,...

    journal_title：Bioorganic chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bioorg.2021.104635

    authors： Dai C,Li X,Zhang K,Li XN,Wang W,Zang Y,Chen X,Li Q,Wei M,Chen C,Zhu H,Zhang Y

    更新日期：2021-01-08 00:00:00