当前位置： SCI文献检索 > BIOORGANIC CHEMISTRY期刊下所有文献 > Molecular-docking-guided design and synthesis of new IAA-tacrine hybrids as multifunctional AChE/BChE inhibitors.

Molecular-docking-guided design and synthesis of new IAA-tacrine hybrids as multifunctional AChE/BChE inhibitors.

Abstract：

:A series of new indole-3-acetic acid (IAA)-tacrine hybrids as dual acetylcholinesterase (AChE)/butyrylcholinesterase (BChE) inhibitors were designed and prepared based on the molecular docking mode of AChE with an IAA derivative (1a), a moderate AChE inhibitor identified by screening our compound library for anti-Alzheimer's disease (AD) drug leads. The enzyme assay results revealed that some hybrids, e.g. 5d and 5e, displayed potent dual in vitro inhibitory activities against AChE/BChE with IC50 values in low nanomolar range. Molecular modeling studies in tandem with kinetic analysis suggest that these hybrids target both catalytic active site and peripheral anionic site of cholinesterase (ChE). Molecular dynamic simulations and Molecular Mechanics/Poisson-Boltzmann Surface Area (MM-PBSA) calculations indicate that 5e has more potent binding affinity than hit 1a, which may explain the stronger inhibitory effect of 5e on AChE. Furthermore, their predicted pharmacokinetic properties and in vitro influences on mouse brain neural network electrical activity were discussed. Taken together, compound 5e can be highlighted as a lead compound worthy of further optimization for designing new anti-AD drugs.

journal_name

Bioorg Chem

journal_title

Bioorganic chemistry

authors

Cheng ZQ,Zhu KK,Zhang J,Song JL,Muehlmann LA,Jiang CS,Liu CL,Zhang H

doi

10.1016/j.bioorg.2018.10.057

subject

Has Abstract

pub_date

2019-03-01 00:00:00

pages

277-288

eissn

0045-2068

issn

1090-2120

pii

S0045-2068(18)30901-5

journal_volume

83

pub_type

杂志文章

相关文献

BIOORGANIC CHEMISTRY文献大全
  • Reconstitution of UDP-galactopyranose mutase with 1-deaza-FAD and 5-deaza-FAD: analysis and mechanistic implications.

    abstract：:The galactofuranose moiety found in many surface constituents of microorganisms is derived from UDP-D-galactopyranose (UDP-Galp) via a unique ring contraction reaction catalyzed by a FAD-dependent UDP-Galp mutase. When the enzyme is reduced by sodium dithionite, its catalytic efficiency increases significantly. Since ...

    journal_title：Bioorganic chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bioorg.2003.08.002

    authors： Huang Z,Zhang Q,Liu HW

    更新日期：2003-12-01 00:00:00

  • Design, synthesis, biological evaluation and in silico studies of novel pyrrolo[3,4-d]pyridazinone derivatives withpromising anti-inflammatory and antioxidant activity.

    abstract：:Novel Mannich base analogues of pyrrolo[3,4-d]pyridazinone 7a,b-13a,b are designed and synthesized as potential anti-inflammatory agents. The title compounds are obtained via convenient one-pot synthesis with good yields. Their structures and properties are described by spectroscopic techniques and elemental analyses....

    journal_title：Bioorganic chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bioorg.2020.104035

    authors： Szczukowski Ł,Redzicka A,Wiatrak B,Krzyżak E,Marciniak A,Gębczak K,Gębarowski T,Świątek P

    更新日期：2020-09-01 00:00:00

  • Scaffold hopping and redesign approaches for quinazoline based urea derivatives as potent VEGFR-2 inhibitors.

    abstract：:In our attempt to discover effective anticancer agents, three series of novel quinazoline-based compounds have been designed, synthesized and tested as VEGFR-2 inhibitors. Five quinazoline -2-carboxamide derivatives (5d, 5e, 5 h, 5i, 5j) revealed potent nanomolar VEGFR-2 inhibition with IC50 values of 12.1, 40.3, 15.5...

    journal_title：Bioorganic chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bioorg.2020.103961

    authors： Hadi SRAE,Lasheen DS,Soliman DH,Elrazaz EZ,Abouzid KAM

    更新日期：2020-08-01 00:00:00

  • Enzymatic mechanisms for catalysis of enolization: ketosteroid isomerase.

    abstract：:Breaking a carbon-hydrogen bond adjacent to a carbonyl is a slow step in a large number of chemical reactions. However, many enzymes are capable of catalyzing this reaction with great efficiency. One of the most proficient of these enzymes is 3-oxo-Delta5-steroid isomerase (KSI), which catalyzes the isomerization of a...

    journal_title：Bioorganic chemistry

    pub_type： 杂志文章,评审

    doi：10.1016/j.bioorg.2004.06.005

    authors： Pollack RM

    更新日期：2004-10-01 00:00:00

  • Bioactivity-based analysis and chemical characterization of hypoglycemic and antioxidant components from Artemisia argyi.

    abstract：:Diabetes is one of the metabolic disorders in the world. It is the prime reason of mortality and morbidity owing to hyperglycemia which is link with numerus obstacles. Artemisia argyi is commonly used as an ingredient in healthy foods as well as an herbal medicine in Asian countries. The present research aims to evalu...

    journal_title：Bioorganic chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bioorg.2019.103268

    authors： Xiao JQ,Liu WY,Sun HP,Li W,Koike K,Kikuchi T,Yamada T,Li D,Feng F,Zhang J

    更新日期：2019-11-01 00:00:00

  • Mechanistic investigations on substituted benzene sulphonamides as apoptosis inducing anticancer agents.

    abstract：:In an approach to develop potent cytotoxic compounds with targeted action, a systematic methodology was employed to design and initially synthesize parent compounds A1, A8, A13 and A14 followed by synthesis of further analogs of A1 (A2-A7) and A8 (A9-A12) with characterization by IR, NMR, mass and elemental techniques...

    journal_title：Bioorganic chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bioorg.2019.103539

    authors： Mettu A,Talla V,Thumma S,Naikal James Prameela S

    更新日期：2020-01-01 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

  • Functional studies of rat hydroxymethylbilane synthase.

    abstract：:The structurally related tetrapyrrolic pigments are a group of natural products that participate in many of the fundamental biosynthetic and catabolic processes of living organisms. Hydroxymethylbilane synthase catalyzes a rate-limiting step for the biosyntheses of tetrapyrrolic natural products. We carried out extens...

    journal_title：Bioorganic chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bioorg.2008.07.001

    authors： Li N,Chu X,Wu L,Liu X,Li D

    更新日期：2008-10-01 00:00:00

  • Design, synthesis, molecular modeling and biological evaluation of novel 1H-pyrazolo[3,4-b]pyridine derivatives as potential anticancer agents.

    abstract：:In trying to develop new anticancer agents, a series of 1H-pyrazolo[3,4-b]pyridine derivatives was designed and synthesized. Fifteen compounds were evaluated in vitro for their anti-proliferative activity against HePG-2, MCF-7, HCT-116, and PC-3 cell lines. Additionally, DNA binding affinity of the synthesized derivat...

    journal_title：Bioorganic chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bioorg.2016.05.006

    authors： Eissa IH,El-Naggar AM,El-Hashash MA

    更新日期：2016-08-01 00:00:00

  • Structural optimization of imidazothiazole derivatives affords a new promising series as B-Raf V600E inhibitors; synthesis, in vitro assay and in silico screening.

    abstract：:BRAF mutation is commonly known in a number of human cancer types. It is counted as a potential component in treating cancer. In this study, based on structural optimization of previously reported inhibitors (3-fluro substituted derivatives of imidazo[2,1-b]thiazole-based scaffold), we designed and synthesized sixteen...

    journal_title：Bioorganic chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bioorg.2020.103967

    authors： Ammar UM,Abdel-Maksoud MS,Ali EMH,Mersal KI,Ho Yoo K,Oh CH

    更新日期：2020-07-01 00:00:00

  • Differential metabolism of diastereoisomeric diterpenes by Preussia minima, found as endophytic fungus in Cupressus lusitanica.

    abstract：:The plant diastereoisomeric diterpenes ent-pimara-8(14)-15-dien-19-oic acid, obtained from Viguiera arenaria, and isopimara-8(14)-15-dien-18-oic acid, isolated from Cupressus lusitanica, were distinctly functionalized by the enzymes produced in whole cell cultures of the fungus Preussia minima, isolated from surface s...

    journal_title：Bioorganic chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bioorg.2018.04.003

    authors： Ud Din Z,de Medeiros LS,Abreu LM,Pfenning LH,Lopes Jymeni DB,Rodrigues-Filho E

    更新日期：2018-08-01 00:00:00

  • In vitro study and structure-activity relationship analysis of stilbenoid derivatives as powerful vasorelaxants: Discovery of new lead compound.

    abstract：:The development of vasorelaxant as the antihypertensive drug is important as it produces a rapid and direct relaxation effect on the blood vessel muscles. Resveratrol (RV), as the most widely studied stilbenoid and the lead compound, inducing the excellent vasorelaxation effect through the multiple signalling pathways...

    journal_title：Bioorganic chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bioorg.2020.104239

    authors： Chan SY,Loh YC,Oo CW,Yam MF

    更新日期：2020-11-01 00:00:00

  • Probing phenylcarbamoylazinane-1,2,4-triazole amides derivatives as lipoxygenase inhibitors along with cytotoxic, ADME and molecular docking studies.

    abstract：:Hunting small molecules as anti-inflammatory agents/drugs is an expanding and successful approach to treat several inflammatory diseases such as cancer, asthma, arthritis, and psoriasis. Besides other methods, inflammatory diseases can be treated by lipoxygenase inhibitors, which have a profound influence on the devel...

    journal_title：Bioorganic chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bioorg.2020.104525

    authors： Muzaffar S,Shahid W,Riaz N,Saleem M,Ashraf M,Aziz-Ur-Rehman,Bashir B,Kaleem A,Al-Rashida M,Baral B,Bhattarai K,Gross H

    更新日期：2020-12-03 00:00:00

  • Kinetic Isotope Effects and Stereochemical Studies on a Ribonuclease Model: Hydrolysis Reactions of Uridine 3'-Nitrophenyl Phosphate.

    abstract：:The reactions of a ribonuclease model substrate, the compound uridine-3'-p-nitrophenyl phosphate, have been examined using heavy-atom isotope effects and stereochemical analysis. The cyclization of this compound is subject to catalysis by general base (by imidazole buffer), specific base (by carbonate buffer), and by ...

    journal_title：Bioorganic chemistry

    pub_type： 杂志文章

    doi：10.1006/bioo.2000.1170

    authors： Hengge AC,Bruzik KS,Tobin AE,Cleland WW,Tsai MD

    更新日期：2000-06-01 00:00:00

  • Syntheses of diacyltanshinol derivatives and their suppressive effects on macrophage foam cell formation by reducing oxidized LDL uptake.

    abstract：:A series of diacyltanshinol derivatives were synthesized by esterifying the corresponding o-hydroquinones of tanshinones. The suppressive effects of the synthesized compounds on oxidized low-density lipoprotein (oxLDL) uptake and oxLDL-induced macrophage-derived foam cell formation were evaluated. Our results indicate...

    journal_title：Bioorganic chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bioorg.2013.11.001

    authors： Cheng X,Zhang DL,Li XB,Ye JT,Shi L,Huang ZS,Gu LQ,An LK

    更新日期：2014-02-01 00:00:00

  • Synthesis of 4,6-dideoxy-3-fluoro-2-keto-beta-D-glucopyranosyl analogues of 5-fluorouracil, N6-benzoyl adenine, uracil, thymine, N4-benzoyl cytosine and evaluation of their antitumor activities.

    abstract：:The synthesis of the unsaturated 4,6-dideoxy-3-fluoro-2-keto-beta-d-glucopyranosyl nucleosides of 5-fluorouracil (6a), N(6)-benzoyl adenine (6b), uracil (6c), thymine (6d) and N(4)-benzoyl cytosine (6e), is described. Monoiodination of compounds 1a,b, followed by acetylation, catalytic hydrogenation and finally regios...

    journal_title：Bioorganic chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bioorg.2009.11.001

    authors： Manta S,Tsoukala E,Tzioumaki N,Kiritsis C,Balzarini J,Komiotis D

    更新日期：2010-04-01 00:00:00

  • Synthesis and tyrosinase inhibitory activity of novel N-hydroxybenzyl-N-nitrosohydroxylamines.

    abstract：:Several novel N-substituted N-nitrosohydroxylamines were synthesized. They all inhibited mushroom tyrosinase, but the type of inhibition was different depending on the substituent. Some N-(mono- or dihydroxybenzyl)-N-nitrosohydroxylamines exhibited uncompetitive inhibition with respect to L-dopa. Among them, compound ...

    journal_title：Bioorganic chemistry

    pub_type： 杂志文章

    doi：10.1016/S0045-2068(03)00026-9

    authors： Shiino M,Watanabe Y,Umezawa K

    更新日期：2003-04-01 00:00:00

  • Building fluorescent sensors for carbohydrates using template-directed polymerizations.

    abstract：:The ability to custom-make fluorescent sensors for different analytes could have a tremendous impact in a variety of areas. Template-directed polymerization or molecular imprinting seems to be a promising approach for the preparation of high-affinity and specific binding sites for different template molecules. However...

    journal_title：Bioorganic chemistry

    pub_type： 杂志文章

    doi：10.1006/bioo.2001.1219

    authors： Gao S,Wang W,Wang B

    更新日期：2001-10-01 00:00:00

  • Novel artemisinin derivatives with potent anticancer activities and the anti-colorectal cancer effect by the mitochondria-mediated pathway.

    abstract：:Many artemisinin derivatives have good inhibitory effects on malignant tumors. In this work, a novel series of artemisinin derivatives containing piperazine and fluorine groups were designed and synthesized and their structures were confirmed by 1H NMR, 13C NMR and HRMS technologies. The in vitro cytotoxicity against ...

    journal_title：Bioorganic chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bioorg.2020.104496

    authors： Lin L,Lu W,Dai T,Chen H,Wang T,Yang L,Yang X,Liu Y,Sun D

    更新日期：2021-01-01 00:00:00

  • New fused pyrimidine derivatives with anticancer activity: Synthesis, topoisomerase II inhibition, apoptotic inducing activity and molecular modeling study.

    abstract：:A new series of triazolopyrimidines and thiazolopyrimidine hydrobromides was designed and prepared as topoisomerase II inhibitors. Screening of all synthesized compounds was carried out by the National Cancer Institute (NCI) of USA. Activity against 60 human cancer cell lines representing different cancer types was de...

    journal_title：Bioorganic chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bioorg.2020.104134

    authors： Nemr MTM,AboulMagd AM

    更新日期：2020-10-01 00:00:00

  • Exploration of aroyl/heteroaroyl iminothiazolines featuring 2,4,5-trichlorophenyl moiety as a new class of potent, selective, and in vitro efficacious glucosidase inhibitors.

    abstract：:A series of iminothiazolines (4a-j) featuring 2,4,5-trichlorophenyl moiety and aroyl/heteroaroyl substituents has been prepared from readily accessible thioureas. In-vitro screening against glucosidase enzymes showed highly specific inhibition of α-glucosidase with a marked dependence of the potency upon the nature of...

    journal_title：Bioorganic chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bioorg.2017.07.012

    authors： Kazmi M,Zaib S,Amjad ST,Khan I,Ibrar A,Saeed A,Iqbal J

    更新日期：2017-10-01 00:00:00

  • Bioactivity and molecular docking studies of some nickel complexes: New analogues for the treatment of Alzheimer, glaucoma and epileptic diseases.

    abstract：:The interaction of the coordination compounds with biological molecules resulted in the investigation of the drug potential of these molecules. In this study, enzyme inhibition of DSA (1-3) coordination compounds that were previously investigated for their anticancer and antibacterial properties was investigated. Also...

    journal_title：Bioorganic chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bioorg.2020.104066

    authors： Kısa D,Korkmaz N,Taslimi P,Tuzun B,Tekin Ş,Karadag A,Şen F

    更新日期：2020-08-01 00:00:00

  • Multi-target 1,4-dihydropyridines showing calcium channel blockade and antioxidant capacity for Alzheimer's disease therapy.

    abstract：:In this work we describe the synthesis, Ca+2 channel blockade capacity and antioxidant power of N3,N5-bis(2-(5-methoxy-1H-indol-3-yl)ethyl)-2,6-dimethyl-4-aryl-1,4-dihydropyridine-3,5-dicarboxamides 1-9, a number of multi-target small 1,4-dihydropyridines (DHP), designed by juxtaposition of melatonin and nimodipine. A...

    journal_title：Bioorganic chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bioorg.2019.103205

    authors： Malek R,Maj M,Wnorowski A,Jóźwiak K,Martin H,Iriepa I,Moraleda I,Chabchoub F,Marco-Contelles J,Ismaili L

    更新日期：2019-10-01 00:00:00

  • Synthesis and biological evaluation of 2-epi-jaspine B analogs as selective sphingosine kinase 1 inhibitors.

    abstract：:2-Epi-jaspine B is an isomer of the natural product jaspine B and shows certain selectivity for SphK1 and potent antitumor activity. Based on the crystal structure of SphK1, we transformed the structure of 2-epi-jaspine B and modified the hydrophobic side chain to obtain a series of 2-epi-jaspine B analogs. The MTT as...

    journal_title：Bioorganic chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bioorg.2019.103369

    authors： Yang H,Li Y,Chai H,Yakura T,Liu B,Yao Q

    更新日期：2020-05-01 00:00:00

  • Synthesis and biological evaluation of bergenin-1,2,3-triazole hybrids as novel class of anti-mitotic agents.

    abstract：:In continuation of our investigation of pharmacologically-motivated natural products, we have isolated bergenin (1) as a major compound from Mallotus philippensis, which is deployed in different Indian traditional systems of medicine. Here, a series of bergenin-1,2,3-triazole hybrids were synthesized and evaluated for...

    journal_title：Bioorganic chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bioorg.2019.103161

    authors： Pavan Kumar P,Siva B,Venkateswara Rao B,Dileep Kumar G,Lakshma Nayak V,Nishant Jain S,Tiwari AK,Purushotham U,Venkata Rao C,Suresh Babu K

    更新日期：2019-10-01 00:00:00

  • Antimycobacterial activity of azepanobetulin and its derivative: In vitro, in vivo, ADMET and docking studies.

    abstract：:The antimycobacterial investigation of azepanobetulin and its amide derivative was performed. Both compounds showed increased in vitro antibacterial activity on the H37Rv MTB strain in aerobic and anaerobic conditions. Basing on differences between MIC and IC50 values a predominant bactericidal effect for amide in con...

    journal_title：Bioorganic chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bioorg.2020.104209

    authors： Kazakova O,Lopatina T,Giniyatullina G,Mioc M,Soica C

    更新日期：2020-11-01 00:00:00

  • Synthesis of some N-aroyl-2-oxindole benzenesulfonamide conjugates with carbonic anhydrase inhibitory activity.

    abstract：:Implication of carbonic anhydrases (CAs) in many physiological functions made them attractive therapeutic targets. Herein, we report the synthesis of three series of benzenesulfonamide-based compounds (5a-e, 9a-e and 10a-e) as potential ligands to four of the human CA isoforms (hCA I, hCA II, hCA IX and hCA XII). All ...

    journal_title：Bioorganic chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bioorg.2020.103635

    authors： George RF,Bua S,Supuran CT,Awadallah FM

    更新日期：2020-03-01 00:00:00

  • Design, synthesis, and biological evaluation of novel dual FFA1 (GPR40)/PPARδ agonists as potential anti-diabetic agents.

    abstract：:The free fatty acid receptor 1 (FFA1) and peroxisome proliferator-activated receptor δ (PPARδ) were considered as potential anti-diabetic targets, and the dual FFA1/PPARδ agonists might provide synergistic effect in insulin secretion and sensibility. Herein, we further develop dual agonists by screening 7 series of he...

    journal_title：Bioorganic chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bioorg.2019.103254

    authors： Li Z,Hu L,Wang X,Zhou Z,Deng L,Xu Y,Zhang L

    更新日期：2019-11-01 00:00:00

  • Evaluation of thioamides, thiolactams and thioureas as hydrogen sulfide (H2S) donors for lowering blood pressure.

    abstract：:Hydrogen sulfide (H2S) is a biologically important gaseous molecule that exhibits promising protective effects against a variety of pathological processes. For example, it was recognized as a blood pressure lowering agent. Aligned with the need for easily modifiable platforms for the H2S supply, we report here the pre...

    journal_title：Bioorganic chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bioorg.2019.102941

    authors： Zaorska E,Hutsch T,Gawryś-Kopczyńska M,Ostaszewski R,Ufnal M,Koszelewski D

    更新日期：2019-07-01 00:00:00

  • Heterocyclic cellular lipid peroxidation inhibitors inspired by the marine antioxidant barettin.

    abstract：:The marine environment remains a rich source for the discovery and development of novel bioactive compounds. The present paper describes the design, synthesis and biological evaluation of a library of small molecule heterocyclic mimetics of the marine 2,5-diketopiperazine barettin which is a powerful natural antioxida...

    journal_title：Bioorganic chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bioorg.2018.11.024

    authors： Labrière C,Andersen JH,Albrigtsen M,Hansen JH,Svenson J

    更新日期：2019-03-01 00:00:00