当前位置： SCI文献检索 > BIOORGANIC & MEDICINAL CHEMISTRY期刊下所有文献 > Design and synthesis of thiazolylhydrazone derivatives as inhibitors of chitinolytic N-acetyl-β-d-hexosaminidase.

Design and synthesis of thiazolylhydrazone derivatives as inhibitors of chitinolytic N-acetyl-β-d-hexosaminidase.

Abstract：

:N-acetyl-β-d-hexosaminidase (Hex) is potential target for pesticide design. Here, a series of thiazolylhydrazone derivatives were designed, synthesized and evaluated as competitive inhibitors of OfHex1, a Hex from the agricultural pest Ostrinia furnacalis. The derivative 3k, with a (benzyloxy)methyl group at the N3 atom, demonstrated greater potency with a Ki of 10.2 µM. Molecular docking analysis indicated that the (benzyloxy)methyl group of 3k was bound to a previously unexplored pocket formed by Loop478-496. Then further optimization around naphthalene ring led to find the more potency substituent phenyl. The derivative 7, with phenoxyethyl group at R1 and a phenyl group at R2, demonstrated an augmented potency with a Ki of 2.1 µM. Molecular docking analysis indicated that 7 was bound to the active pocket of OfHex1 more favorably than 3k. This work suggests a novel scaffold for developing specific Hex inhibitors.

journal_name

Bioorg Med Chem

journal_title

Bioorganic & medicinal chemistry

authors

Yang H,Liu T,Qi H,Huang Z,Hao Z,Ying J,Yang Q,Qian X

doi

10.1016/j.bmc.2018.09.014

subject

Has Abstract

pub_date

2018-11-01 00:00:00

pages

5420-5426

issue

20

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(18)31174-X

journal_volume

26

pub_type

杂志文章

相关文献

BIOORGANIC & MEDICINAL CHEMISTRY文献大全
  • Identification of topoisomerases as molecular targets of cytosporolide C and its analog.

    abstract：:Cytosporolide (Cytos) A-C, isolated from the fungus Cytospora sp., have anti-microbial activity, but their molecular targets in mammalian cells are unknown. We have previously reported the total synthesis of Cytos A by biomimetic hetero-Diels-Alder reaction. In this study, to examine the novel bioactivity of Cytos, we...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2019.06.014

    authors： Otake K,Yamada K,Miura K,Sasazawa Y,Miyazaki S,Niwa Y,Ogura A,Takao KI,Simizu S

    更新日期：2019-08-01 00:00:00

  • N-aroyloxylthioxo-naphthalimides as DNA photocleavers of aroyloxyl oxygen radicals: synthesis, evaluation, and substituents' effect.

    abstract：:Novel N-Aroyloxylthioxo-naphthalimides as highly efficient 'time-resolved' DNA photocleavers of aroyloxyl radicals type were designed and synthesized. The substituents at the aroyloxyl moiety have an important and unusual influence on the DNA photocleavage, and DNA photodamages of the compounds were unusually not depe...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2004.02.013

    authors： Xu Y,Huang X,Qian X,Yao W

    更新日期：2004-05-01 00:00:00

  • Syntheses and receptor-binding studies of derivatives of the opioid antagonist naltrexone.

    abstract：:Naltrexone (1), which is a member of the group of competitive opioid antagonists, shows a strong affinity for mu-receptors and its derivatives have been notable as novel receptor antagonists. In this paper, the preparation of several naltrexone derivatives is described; these were used to investigate the role of the o...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2003.10.039

    authors： Uwai K,Uchiyama H,Sakurada S,Kabuto C,Takeshita M

    更新日期：2004-01-15 00:00:00

  • Acetylcholinesterase inhibitors from the toadstool Cortinarius infractus.

    abstract：:Inhibition of acetylcholinesterase (AChE) and therefore prevention of acetylcholine degradation is one of the most accepted therapy opportunities for Alzheimer s disease (AD), today. Due to lack of selectivity of AChE inhibitor drugs on the market, AD-patients suffer from side effects like nausea or vomiting. In the p...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2010.01.074

    authors： Geissler T,Brandt W,Porzel A,Schlenzig D,Kehlen A,Wessjohann L,Arnold N

    更新日期：2010-03-15 00:00:00

  • Catechol derivatives of aminopyrazine and cell protection against UVB-induced mortality.

    abstract：:A series of 5-aryl- and 3,5-bis-aryl-2-amino-1,4-pyrazine derivatives 4 and 6, and related imidazolopyrazinones 7, has been synthesized, the aryl groups of which are catechol and/or phenol substituents. These compounds, tested against human keratinocyte cells stressed by UVB irradiation, showed high antioxidative prop...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0968-0896(00)00321-7

    authors： Cavalier JF,Burton M,Dussart F,Marchand C,Rees JF,Marchand-Brynaert J

    更新日期：2001-04-01 00:00:00

  • Anti-HIV diarylpyrimidine-quinolone hybrids and their mode of action.

    abstract：:A molecular hybridization approach is a powerful tool in the design of new molecules with improved affinity and efficacy. In this context, a series of diarylpyrimidine-quinolone hybrids were synthesized and evaluated against both wt HIV-1 and mutant viral strains. The most active hybrid 5a displayed an EC50 value of 0...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2015.03.037

    authors： Mao TQ,He QQ,Wan ZY,Chen WX,Chen FE,Tang GF,De Clercq E,Daelemans D,Pannecouque C

    更新日期：2015-07-01 00:00:00

  • Design and synthesis of novel pyrimido[4,5-b]azepine derivatives as HER2/EGFR dual inhibitors.

    abstract：:A novel 7,6 fused bicyclic scaffold, pyrimido[4,5-b]azepine was designed to fit into the ATP binding site of the HER2/EGFR proteins. The synthesis of this scaffold was accomplished by an intramolecular Claisen-type condensation. As the results of optimization lead us to 4-anilino and 6-functional groups, we discovered...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2013.02.014

    authors： Kawakita Y,Seto M,Ohashi T,Tamura T,Yusa T,Miki H,Iwata H,Kamiguchi H,Tanaka T,Sogabe S,Ohta Y,Ishikawa T

    更新日期：2013-04-15 00:00:00

  • Exploring a synthetic organoselenium compound for antioxidant pharmacotherapy--toxicity and effects on ROS-production.

    abstract：:The organoselenium antioxidant 1 was previously found to act as a catalytic antioxidant in a two-phase lipid peroxidation system. In aqueous environment, selenide 1 quenched ABTS-radicals more efficiently than Trolox and ascorbic acid. The selenide dose-dependently scavenged reactive oxygen and nitrogen species more e...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2010.01.057

    authors： Johansson H,Svartström O,Phadnis P,Engman L,Ott MK

    更新日期：2010-03-01 00:00:00

  • Comparison in antioxidant action between α-chitosan and β-chitosan at a wide range of molecular weight and chitosan concentration.

    abstract：:Antioxidant activity in α- and β-chitosan at a wide range of molecular weight (Mw) and chitosan concentration (CS) was determined by 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity, reducing ability, chelating ability, and hydroxyl radical scavenging activity. The form of chitosan (FC) had significant...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2012.03.020

    authors： Jung J,Zhao Y

    更新日期：2012-05-01 00:00:00

  • Synthesis and biological evaluation of novel pyrazolyl-2,4-thiazolidinediones as anti-inflammatory and neuroprotective agents.

    abstract：:Novel pyrazolyl-2,4-thiazolidinediones were prepared via the reaction of appropriate pyrazolecarboxaldehydes with 2,4-thiazolidinediones and substituted benzyl-2,4-thiazolidinediones. The resultant compounds were first evaluated for their anti-inflammatory and neuroprotective properties in vitro. The active compounds ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2010.01.021

    authors： Youssef AM,White MS,Villanueva EB,El-Ashmawy IM,Klegeris A

    更新日期：2010-03-01 00:00:00

  • 2-N-Methyl modifications and SAR studies of manzamine A.

    abstract：:Quaternary carbolinium salts have been reported to show improved antimalarial activity and reduced cytotoxicity as compared to electronically neutral beta-carbolines. In this study, mono- and di-methylated quaternary carbolinium cations of manzamine A were synthesized and evaluated for their in vitro antimalarial and ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2008.05.079

    authors： Ibrahim MA,Shilabin AG,Prasanna S,Jacob M,Khan SI,Doerksen RJ,Hamann MT

    更新日期：2008-07-15 00:00:00

  • A novel non-stochastic quadratic fingerprints-based approach for the 'in silico' discovery of new antitrypanosomal compounds.

    abstract：:A non-stochastic quadratic fingerprints-based approach is introduced to classify and design, in a rational way, new antitrypanosomal compounds. A data set of 153 organic chemicals, 62 with antitrypanosomal activity and 91 having other clinical uses, was processed by a k-means cluster analysis to design training and pr...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2005.06.049

    authors： Montero-Torres A,Vega MC,Marrero-Ponce Y,Rolón M,Gómez-Barrio A,Escario JA,Arán VJ,Martínez-Fernández AR,Meneses-Marcel A

    更新日期：2005-11-15 00:00:00

  • Structural insights into the hot spot amino acid residues of mushroom tyrosinase for the bindings of thujaplicins.

    abstract：:Tyrosinase inhibitors are important agents for cosmetic products. We examined here the inhibitory effects of three isomers of thujaplicins (α, β and γ) on mushroom tyrosinase and analyzed their binding modes using a homology model from the crystal structure of Streptomyces castaneoglobisporus tyrosinase (PDB ID: 1wx2)...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2010.08.056

    authors： Takahashi S,Kamiya T,Saeki K,Nezu T,Takeuchi S,Takasawa R,Sunaga S,Yoshimori A,Ebizuka S,Abe T,Tanuma S

    更新日期：2010-11-15 00:00:00

  • PET-compatible endothelin receptor radioligands: synthesis and first in vitro and in vivo studies.

    abstract：:The expression and function of endothelin (ET) receptors is abnormal in cardiovascular diseases, tumor progression, and tumor metastasis. In this study, we prepared two [(18)F]-fluorinated derivatives of the non-peptide ET(A) receptor antagonist PD 156707 and evaluated their ET receptor binding potencies. Ex vivo as w...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2009.08.058

    authors： Höltke C,Law MP,Wagner S,Kopka K,Faust A,Breyholz HJ,Schober O,Bremer C,Riemann B,Schäfers M

    更新日期：2009-10-15 00:00:00

  • Design, synthesis, and binding of homologated truncated 4'-thioadenosine derivatives at the human A3 adenosine receptors.

    abstract：:We synthesized homologated truncated 4'-thioadenosine analogues 3 in which a methylene (CH(2)) group was inserted in place of the glycosidic bond of a potent and selective A(3) adenosine receptor antagonist 2. The analogues were designed to induce maximum binding interaction in the binding site of the A(3) adenosine r...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2010.08.018

    authors： Lee HW,Kim HO,Choi WJ,Choi S,Lee JH,Park SG,Yoo L,Jacobson KA,Jeong LS

    更新日期：2010-10-01 00:00:00

  • Synthesis and cancer cell cytotoxicity of substituted xanthenes.

    abstract：:A series of substituted xanthenes was synthesized and screened for activity using DU-145, MCF-7, and HeLa cancer cell growth inhibition assays. The most potent compound, 9 g ([N,N-diethyl]-9-hydroxy-9-(3-methoxyphenyl)-9H-xanthene-3-carboxamide), was found to inhibit cancer cell growth with IC(50) values ranging from ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2010.01.018

    authors： Giri R,Goodell JR,Xing C,Benoit A,Kaur H,Hiasa H,Ferguson DM

    更新日期：2010-02-15 00:00:00

  • 3-Aza-6,8-dioxabicyclo[3.2.1]octanes as new enantiopure heteroatom-rich tropane-like ligands of human dopamine transporter.

    abstract：:CNS diseases such as Parkinson, schizophrenia, and attention deficit hyperactivity disorder (ADHD) are characterized by a significant alteration of dopamine transporter (DAT) density. Thus, the development of compounds that are able to selectively interact with DAT is of great interest. Herein we describe the design a...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2006.04.019

    authors： Cini N,Danieli E,Menchi G,Trabocchi A,Bottoncetti A,Raspanti S,Pupi A,Guarna A

    更新日期：2006-08-01 00:00:00

  • Synthesis and anti-influenza virus activity of dihydrofuran-fused perhydrophenanthrenes with a benzyloxy-type side-chain.

    abstract：:As one of our ongoing research project concerning development of a novel anti-influenza virus agent, dihydrofuran-fused perhydrophenanthrenes were derivatized by means of Williamson ether synthesis and Suzuki-Miyaura cross coupling reactions. Newly synthesized compounds were subjected to evaluation of anti-influenza v...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2010.01.014

    authors： Matsuya Y,Suzuki N,Kobayashi SY,Miyahara T,Ochiai H,Nemoto H

    更新日期：2010-02-15 00:00:00

  • Polymer-bound reagents for the introduction of spacer-modified biotin labels.

    abstract：:We have developed a method for the chemoselective introduction of spacer modified biotin labels into unprotected multi-functional amines. A range of novel biotin spacer conjugates attached to a polymer-bound sulfonamide anchor was prepared using established amide bond forming procedures. After chemical transformation ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2004.03.038

    authors： Herforth C,Heidler P,Franke S,Link A

    更新日期：2004-06-01 00:00:00

  • Discovery and structure-activity relationship studies of quinolinone derivatives as potent IL-2 suppressive agents.

    abstract：:The quinolinone skeleton has been utilized to develop various mechanism-based immune modulators. However, the effects of quinolinone derivatives on the release of T cell-associated interleukin-2 (IL-2) have not been established. In this study, a series of novel quinolinone derivatives was synthesized, and their immuno...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2016.08.051

    authors： Kwak SH,Kang JA,Kim M,Lee SD,Park JH,Park SG,Ko H,Kim YC

    更新日期：2016-11-01 00:00:00

  • Syntheses and molecular structures of 3-N, N-di-n-propylamino-2-chromanones as new analogues of dopamine.

    abstract：:A series of 3-N,N-di-n-propylamino-2-chromanones were synthesized as dopamine analogues. The lactone ring was introduced as a means to reduce their propensity to cross the blood-brain barrier and to avoid central side effects, rendering these compounds potentially useful for the treatment of glaucoma. Pharmacological ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/0968-0896(95)00154-9

    authors： Benoit-Guyod M,Nicolle E,Namil A,Coulombeau C,Leclerc G

    更新日期：1995-12-01 00:00:00

  • Synthesis of 5-arylidene-2-amino-4-azolones and evaluation of their anticancer activity.

    abstract：:Series of novel 5-arylidene-2-arylaminothiazol-4(5H)-ones and 2-aryl(benzyl)amino-1H-imidazol-4(5H)-ones were synthesized from appropriate 2-alkylthioazol-4-ones using nucleophilic substitution in position 2 by various anilines and benzylamines and Knoevenagel reaction. X-ray structural studies of 22 revealed the stru...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2010.05.073

    authors： Subtel'na I,Atamanyuk D,Szymańska E,Kieć-Kononowicz K,Zimenkovsky B,Vasylenko O,Gzella A,Lesyk R

    更新日期：2010-07-15 00:00:00

  • Quantitative structure-activity relationships of 1,3,4-thiadiazol-2(3H)-ones and 1,3,4-oxadiazol-2(3H)-ones as human protoporphyrinogen oxidase inhibitors.

    abstract：:Protoporphyrinogen oxidase (Protox, EC 1.3.3.4) has attracted great interest during the last decades due to its unique biochemical characteristics and biomedical significance. As a continuation of our research work on the development of new PPO inhibitors, 23 new 1,3,4-thiadiazol-2(3H)-ones bearing benzothiazole subst...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2011.10.079

    authors： Zuo Y,Yang SG,Jiang LL,Hao GF,Wang ZF,Wu QY,Xi Z,Yang GF

    更新日期：2012-01-01 00:00:00

  • Relationship between structure and permeability of dipeptide derivatives containing tryptophan and related compounds across human intestinal epithelial (Caco-2) cells.

    abstract：:The permeability of dipeptide derivatives containing tryptophans and indole derivatives through Caco-2 cells was used as an in vitro intestinal absorption model in order to clarify structural factors which influence their intestinal epithelial permeation and metabolism. Most peptide derivatives were hydrolysed not onl...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2003.10.001

    authors： Ano R,Kimura Y,Urakami M,Shima M,Matsuno R,Ueno T,Akamatsu M

    更新日期：2004-01-02 00:00:00

  • In vitro activity of novel dual action MDR anthranilamide modulators with inhibitory activity on CYP-450 (Part 2).

    abstract：:Synthesis and in vitro cytotoxicity assays of new anthranilamide MDR modulators have been performed to assess their inhibition potency on the P-glycoprotein (P-gp) transporter. Previous studies showed that the replacement of the aromatic spacer group between nitrogen atoms (N(1) and N(2)) in the P-gp inhibitor XR9576 ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2007.03.014

    authors： Labrie P,Maddaford SP,Lacroix J,Catalano C,Lee DK,Rakhit S,Gaudreault RC

    更新日期：2007-06-01 00:00:00

  • A strategic approach to the synthesis of ferrocene appended chalcone linked triazole allied organosilatranes: Antibacterial, antifungal, antiparasitic and antioxidant studies.

    abstract：:A series of ferrocene appended chalcone allied triazole coupled organosilatranes (FCTSa 7-FCTSa 12) were synthesised with the aim of amalgamating the pharmacological action of the constituting moieties into a single molecular scaffold. All the synthesised silatranes were well characterized by various spectroscopic tec...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2018.11.038

    authors： Singh G,Arora A,Kalra P,Maurya IK,Ruizc CE,Estebanc MA,Sinha S,Goyal K,Sehgal R

    更新日期：2019-01-01 00:00:00

  • Structural analogues of the natural products magnolol and honokiol as potent allosteric potentiators of GABA(A) receptors.

    abstract：:Biphenylic compounds related to the natural products magnolol and 4'-O-methylhonokiol were synthesized, evaluated and optimized as positive allosteric modulators (PAMs) of GABA(A) receptors. The most efficacious compounds were the magnolol analog 5-ethyl-5'-hexylbiphenyl-2,2'-diol (45) and the honokiol analogs 4'-meth...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2014.10.027

    authors： Fuchs A,Baur R,Schoeder C,Sigel E,Müller CE

    更新日期：2014-12-15 00:00:00

  • Design, synthesis and biological evaluation of novel 4-phenoxy-6,7-disubstituted quinolines possessing (thio)semicarbazones as c-Met kinase inhibitors.

    abstract：:In continuing our efforts to identify small molecules able to inhibit c-Met kinase, three series of novel 6,7-disubstituted-4-phenoxyquinoline derivatives (23a-w, 26a-d and 30a-d) bearing (thio)semicarbazone scaffold were designed, synthesized and evaluated for their cytotoxicity. The biological data revealed that mos...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2016.02.003

    authors： Zhai X,Bao G,Wang L,Cheng M,Zhao M,Zhao S,Zhou H,Gong P

    更新日期：2016-03-15 00:00:00

  • N-Alkenyl and cycloalkyl carbamates as dual acting histamine H3 and H4 receptor ligands.

    abstract：:Previous studies have shown that several imidazole derivatives possess affinity to histamine H(3) and H(4) receptors. Continuing our study on structural requirements responsible for affinity and selectivity for H(3)/H(4) receptor subtypes, two series of 3-(1H-imidazol-4-yl)propyl carbamates were prepared: a series of ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2011.03.046

    authors： Więcek M,Kottke T,Ligneau X,Schunack W,Seifert R,Stark H,Handzlik J,Kieć-Kononowicz K

    更新日期：2011-05-01 00:00:00

  • Solid phase synthesis and antiprotozoal evaluation of di- and trisubstituted 5'-carboxamidoadenosine analogues.

    abstract：:The rapid increase of resistance to drugs commonly used in the treatment of tropical diseases such as malaria and African sleeping sickness calls for the prompt development of new safe and efficacious drugs. The pathogenic protozoan parasites lack the capability of synthesising purines de novo and they take up preform...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2005.10.011

    authors： Rodenko B,Detz RJ,Pinas VA,Lambertucci C,Brun R,Wanner MJ,Koomen GJ

    更新日期：2006-03-01 00:00:00