当前位置： SCI文献检索 > BIOORGANIC CHEMISTRY期刊下所有文献 > Novel cytisine derivatives exert anti-liver fibrosis effect via PI3K/Akt/Smad pathway.

Novel cytisine derivatives exert anti-liver fibrosis effect via PI3K/Akt/Smad pathway.

Abstract：

:A series of new cytisine derivatives with a unique endocyclic scaffold were synthesized and evaluated for their inhibitory effect on collagen α1 (I) (COL1A1) promotor in human LX2 cells, taking cytisine as the lead. Structure-activity relationship (SAR) revealed that introducing a 12N-benzyl substitution might significantly enhance the activity. Compound 5f exhibited a promising inhibitory potency against COL1A1 with an IC50 value of 12.8 μM in human LX2 cells, and an inspiring inhibition activity against COL1A1 on both mRNA and protein levels. It also effectively inhibited the expression of α smooth muscle actin (α-SMA), connective tissue growth factor (CTGA), matrix metalloprotein 2 (MMP-2), and transforming growth factor β1 (TGFβ1), indicating an extensive inhibitory effect against fibrogenetic proteins. In addition, compound 5f displayed reasonable PK and safety profiles. The primary mechanism study indicated that it might repress the hepatic fibrogenesis via PI3K/Akt/Smad signaling pathway. The results provided powerful information for further structure optimization, and compound 5f was selected as a novel anti-liver fibrosis agent for further investigation.

journal_name

Bioorg Chem

journal_title

Bioorganic chemistry

authors

Tang S,Li Y,Bao Y,Dai Z,Niu T,Wang K,He H,Song D

doi

10.1016/j.bioorg.2019.103032

subject

Has Abstract

pub_date

2019-09-01 00:00:00

pages

103032

eissn

0045-2068

issn

1090-2120

pii

S0045-2068(19)30510-3

journal_volume

90

pub_type

杂志文章

相关文献

BIOORGANIC CHEMISTRY文献大全
  • 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

  • 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

  • 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 1-benzyl-1H-benzimidazoles as galectin-1 mediated anticancer agents.

    abstract：:In our pursuit to develop novel non-carbohydrate small molecule Galectin-1 Inhibitors, we have designed a series of 1-benzyl-1H-benzimidazole derivatives and demonstrated their anticancer activity. The compound 6g, 4-(1-benzyl-5-chloro-1H-benzo[d]imidazol-2-yl)-N-(4-hydroxyphenyl) benzamide was found to be most potent...

    journal_title：Bioorganic chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bioorg.2019.103016

    authors： Goud NS,Ghouse SM,Vishnu J,Komal D,Talla V,Alvala R,Pranay J,Kumar J,Qureshi IA,Alvala M

    更新日期：2019-08-01 00:00:00

  • Structure-activity relationships of rationally designed AMACR 1A inhibitors.

    abstract：:α-Methylacyl-CoA racemase (AMACR; P504S) is a promising novel drug target for prostate and other cancers. Assaying enzyme activity is difficult due to the reversibility of the 'racemisation' reaction and the difficulties in the separation of epimeric products; consequently few inhibitors have been described and no str...

    journal_title：Bioorganic chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bioorg.2018.04.024

    authors： Yevglevskis M,Lee GL,Nathubhai A,Petrova YD,James TD,Threadgill MD,Woodman TJ,Lloyd MD

    更新日期：2018-09-01 00:00:00

  • Synthesis of N-2(5H)-furanonyl sulfonyl hydrazone derivatives and their biological evaluation in vitro and in vivo activity against MCF-7 breast cancer cells.

    abstract：:A series of (E)-N-2(5H)-furanonyl sulfonyl hydrazone derivatives have been rationally designed and efficiently synthesized by one-pot reaction with good yields for the first time. This green approach with wide substrate range and good selectivity can be achieved at room temperature in a short time in the presence of m...

    journal_title：Bioorganic chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bioorg.2020.104518

    authors： Yang K,Yang JQ,Luo SH,Mei WJ,Lin JY,Zhan JQ,Wang ZY

    更新日期：2020-11-27 00:00:00

  • Synthesis and biological evaluation of some N-(3-(1H-tetrazol-5-yl) phenyl)acetamide derivatives as novel non-carboxylic PTP1B inhibitors designed through bioisosteric modulation.

    abstract：:Described herein is the synthesis and biological evaluation of a series of non-carboxylic inhibitors of Protein Tyrosine Phosphatase 1B designed using bioisosteric replacement strategy. Six N-(3-(1H-tetrazol-5-yl)phenyl)acetamide derivatives designed employing the aforementioned strategy were synthesized and screened ...

    journal_title：Bioorganic chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bioorg.2018.06.016

    authors： Maheshwari N,Karthikeyan C,Bhadada SV,Sahi C,Verma AK,Hari Narayana Moorthy NS,Trivedi P

    更新日期：2018-10-01 00:00:00

  • 2-Aryl benzazole derived new class of anti-tubercular compounds: Endowed to eradicate mycobacterium tuberculosis in replicating and non-replicating forms.

    abstract：:The high mortality rate and the increasing prevalence of Mtb resistance are the major concerns for the Tuberculosis (TB) treatment in this century. To counteract the prevalence of Mtb resistance, we have synthesized 2-aryl benzazole based dual targeted molecules. Compound 9m and 9n were found to be equally active agai...

    journal_title：Bioorganic chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bioorg.2020.104170

    authors： Velappan AB,Datta D,Ma R,Rana S,Ghosh KS,Hari N,Franzblau SG,Debnath J

    更新日期：2020-10-01 00:00:00

  • Potent human dihydroorotate dehydrogenase inhibitory activity of new quinoline-4-carboxylic acids derived from phenolic aldehydes: Synthesis, cytotoxicity, lipophilicity and molecular docking studies.

    abstract：:A series of novel 2-substituted quinoline-4-carboxylic acids was synthesized by Doebner reaction starting from freely available protocatechuic aldehyde and vanillin precursors. Human dihydroorotate dehydrogenase (hDHODH) was recognised as a clear molecular target for these heterocycles. All compounds were also tested ...

    journal_title：Bioorganic chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bioorg.2020.104373

    authors： Petrović MM,Roschger C,Chaudary S,Zierer A,Mladenović M,Jakovljević K,Marković V,Botta B,Joksović MD

    更新日期：2020-12-01 00:00:00

  • Current development of 5-nitrofuran-2-yl derivatives as antitubercular agents.

    abstract：:Pulmonary tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (MTB) and still remains one of the foremost fatal infectious diseases, infecting nearly a third of the worldwide population. The emergencies of multidrug-resistant and extensively drug-resistant tuberculosis (MDR and XDR-TB) prom...

    journal_title：Bioorganic chemistry

    pub_type： 杂志文章,评审

    doi：10.1016/j.bioorg.2019.102969

    authors： Elsaman T,Mohamed MS,Mohamed MA

    更新日期：2019-07-01 00:00:00

  • Design, synthesis and pharmacological evaluation of 6,7-disubstituted-4-phenoxyquinoline derivatives as potential antitumor agents.

    abstract：:Two series of 6,7-disubstituted-4-phenoxyquinoline derivatives bearing 2,4-imidazolinedione/pyrazolone scaffold were designed, synthesized and evaluated for their c-Met kinase inhibition and cytotoxicity against HT-29, H460, A549, MKN-45, and U87MG cancer cell lines in vitro. The pharmacological data indicated that mo...

    journal_title：Bioorganic chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bioorg.2014.07.011

    authors： Zhou S,Ren J,Liu M,Ren L,Liu Y,Gong P

    更新日期：2014-12-01 00:00:00

  • Design, synthesis, biological evaluation and molecular docking studies of novel benzofuran-pyrazole derivatives as anticancer agents.

    abstract：:This study deals with design and synthesis of novel benzofuran-pyrazole hybrids as anticancer agents. Eight compounds were chosen by National Cancer Institute (NCI), USA to evaluate their in vitro antiproliferative activity at 10(-5)M in full NCI 60 cell panel. The preliminary screening of the tested compounds showed ...

    journal_title：Bioorganic chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bioorg.2015.08.006

    authors： Abd El-Karim SS,Anwar MM,Mohamed NA,Nasr T,Elseginy SA

    更新日期：2015-12-01 00:00:00

  • Discovery of 7H-pyrrolo[2,3-d]pyridine derivatives as potent FAK inhibitors: Design, synthesis, biological evaluation and molecular docking study.

    abstract：:Focal adhesion kinase (FAK) is an intracellular non-receptor tyrosine kinase responsible for development of various tumor types. Aiming to explore new potent inhibitors, two series of 2,4-disubstituted-7H-pyrrolo[2,3-d]pyrimidine derivatives were designed and synthesized on the base of structure-based design strategy....

    journal_title：Bioorganic chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bioorg.2020.104092

    authors： Wang R,Zhao X,Yu S,Chen Y,Cui H,Wu T,Hao C,Zhao D,Cheng M

    更新日期：2020-09-01 00:00:00

  • Benzoxaboroles as dynamic covalent receptors for bioconjugation and transport of nucleosides and related drugs: Proof of action in HeLa cells.

    abstract：:In this work we describe not previously explored binding studies on the reversible interaction of benzoxaborole with ligands of medical and pharmaceutical interest such as nucleosidic drugs gemcitabine and capecitabine, as well as the hydrophobic chemotherapeutic doxorubicin. We include functional derivatives of benzo...

    journal_title：Bioorganic chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bioorg.2019.103059

    authors： Samaniego Lopez C,Martínez JH,Acebedo SL,Spagnuolo CC

    更新日期：2019-09-01 00:00:00

  • Development of pyridazine derivatives as potential EGFR inhibitors and apoptosis inducers: Design, synthesis, anticancer evaluation, and molecular modeling studies.

    abstract：:Novel hybrids of pyridazine-pyrazoline were synthesized aiming to develop new antiproliferative candidates. All compounds were submitted to the National Cancer Institute (NCI), USA, and many were proved to have significant antiproliferative activity. In addition, in vitro studies of the epidermal growth factor recepto...

    journal_title：Bioorganic chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bioorg.2020.104473

    authors： Ahmed MF,Santali EY,Mohi El-Deen EM,Naguib IA,El-Haggar R

    更新日期：2021-01-01 00:00:00

  • Discovery of novel quinazolines as potential anti-tubulin agents occupying three zones of colchicine domain.

    abstract：:A series of novel quinazolines as tubulin inhibitors occupying three zones of colchicine domain have been designed and synthesized inspired by the recently disclosed crystal structure of verubulin analogue 6 with tubulin. Among the newly synthesized compounds, 19c showed noteworthy potency against K562, HepG2, KB, HCT...

    journal_title：Bioorganic chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bioorg.2018.10.027

    authors： Li W,Yin Y,Shuai W,Xu F,Yao H,Liu J,Cheng K,Xu J,Zhu Z,Xu S

    更新日期：2019-03-01 00:00:00

  • Hydrogen transfer pathways of the asymmetric reduction of alpha,beta-unsaturated ketone mediated by baker's yeast.

    abstract：:The hydrogen transfer mechanism of cofactor reduction and recycling processes in the yeast reduction of alpha,beta-unsaturated ketone was studied by using quantitative isotope tracing close to natural abundance measured by (2)H NMR. In the reaction, the active cofactor is NADPH. The cofactor-transferred hydride attack...

    journal_title：Bioorganic chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bioorg.2006.04.002

    authors： Chu Y,Zhang BL,Silvestre V,Cheng JP

    更新日期：2006-06-01 00:00:00

  • Enantiodiscrimination of bilirubin-IXalpha enantiomers in biomembrane models: has chirality a role in bilirubin toxicity?

    abstract：:Simple biomembrane models, namely micellar aggregates formed by enantiopure sodium N-acylprolinates, are able to convert the racemic mixture of bilirubin-IXalpha into an enantiomerically enriched mixture, thus suggesting a possible role of chirality in bilirubin toxicity due to the perturbation of neuron membrane dyna...

    journal_title：Bioorganic chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bioorg.2008.05.001

    authors： Ceccacci F,Giansanti L,Mortera SL,Mancini G,Sorrenti A,Villani C

    更新日期：2008-10-01 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

  • 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

  • Structure-activity relationships and molecular docking of thirteen synthesized flavonoids as horseradish peroxidase inhibitors.

    abstract：:For the first time, the structure-activity relationships of thirteen synthesized flavonoids have been investigated by evaluating their ability to modulate horseradish peroxidase (HRP) catalytic activity. Indeed, a modified spectrophotometrically method was carried out and optimized using 4-methylcatechol (4-MC) as per...

    journal_title：Bioorganic chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bioorg.2017.08.001

    authors： Mahfoudi R,Djeridane A,Benarous K,Gaydou EM,Yousfi M

    更新日期：2017-10-01 00:00:00

  • Synthesis and antimicrobial evaluation of farnesyl diphosphate mimetics.

    abstract：:The synthesis and first antimicrobial evaluation of farnesyl diphosphate mimetics are described. Several analogues (10, 12, 13, and 20) are inhibitors of Candida albicans, Shizosaccharomyces pombe, and Saccharomyces cerevisiae. The activities of analogues 10, 12, and 13, which contain a omega-phenyl moiety and a dipho...

    journal_title：Bioorganic chemistry

    pub_type： 杂志文章

    doi：10.1016/s0045-2068(03)00025-7

    authors： Fairlamb IJ,Dickinson JM,O'Connor R,Cohen LH,van Thiel CF

    更新日期：2003-02-01 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

  • Withanolides from Physalis peruviana showing nitric oxide inhibitory effects and affinities with iNOS.

    abstract：:A phytochemical study to obtain new nitric oxide (NO) inhibitors resulted in the isolation of five new withanolides from the whole plants of Physalis peruviana. The structures were determined on the basis of extensive NMR spectroscopic data analysis as well as the time-dependent density functional theory (TDDFT) elect...

    journal_title：Bioorganic chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bioorg.2019.03.051

    authors： Dong B,An L,Yang X,Zhang X,Zhang J,Tuerhong M,Jin DQ,Ohizumi Y,Lee D,Xu J,Guo Y

    更新日期：2019-06-01 00:00:00

  • Aryl- or heteroaryl-based hydrazinylphthalazine derivatives as new potential antitrypanosomal agents.

    abstract：:A series of twenty phthalazinyl-hydrazones were synthesized and tested as potential anti-Trypanosoma cruzi agents. The phthalazines containing 5-nitroheteroaryl moiety 3l and 3m displayed an excellent in vitro antitrypanosomal profile, exhibiting low micromolar EC50 values against proliferative epimastigote of T. cruz...

    journal_title：Bioorganic chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bioorg.2017.03.008

    authors： Romero AH,Rodríguez J,García-Marchan Y,Leañez J,Serrano-Martín X,López SE

    更新日期：2017-06-01 00:00:00

  • Synthesis and characterization of CAPE derivatives as xanthine oxidase inhibitors with radical scavenging properties.

    abstract：:Inhibitors of the enzyme xanthine oxidase (XO) with radical scavenging properties hold promise as novel agents against reperfusion injuries after ischemic events. By suppressing the formation of damaging reactive oxygen species (ROS) by XO or scavenging ROS from other sources, these compounds may prevent a buildup of ...

    journal_title：Bioorganic chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bioorg.2019.02.049

    authors： Choi W,Villegas V,Istre H,Heppler B,Gonzalez N,Brusman N,Snider L,Hogle E,Tucker J,Oñate A,Oñate S,Ma L,Paula S

    更新日期：2019-05-01 00:00:00

  • A structure-activity relationship study of Forkhead Domain Inhibitors (FDI): The importance of halogen binding interactions.

    abstract：:The Forkhead boX M1 (FOXM1) protein is an essential transcription factor required for the normal activation of human cell cycle. However, increasing evidence supports a correlation between FOXM1 overexpression and the onset of several types of cancer. Based on a previously reported molecular modeling and molecular dyn...

    journal_title：Bioorganic chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bioorg.2019.103269

    authors： Tabatabaei Dakhili SA,Pérez DJ,Gopal K,Tabatabaei Dakhili SY,Ussher JR,Velázquez-Martínez CA

    更新日期：2019-12-01 00:00:00

  • Application of carbamyl in structural optimization.

    abstract：:Carbamyl is considered a privileged structure in medicinal chemistry. It has a wide range of biological activities such as antimicrobial, anticancer, anti-epilepsy, for which the best evidence is a number of marketed carbamyl-containing drugs. Carbamyl is formed of primary amine and carbonyl moieties that act as hydro...

    journal_title：Bioorganic chemistry

    pub_type： 杂志文章,评审

    doi：10.1016/j.bioorg.2020.103757

    authors： Wang K,Zhu H,Zhao H,Zhang K,Tian Y

    更新日期：2020-05-01 00:00:00

  • Design, synthesis, and biological evaluation of novel imidazole derivatives possessing terminal sulphonamides as potential BRAFV600Einhibitors.

    abstract：:BRAFV600E mutation has been detected in various malignant tumours. Developing of potent BRAFV600E inhibitors is considered a leading step in the way to cure different cancer types. In the current work, a series of 38 4-(1H-imidazol-5-yl)pyridin-2-amine derivatives was designed and synthesized using Dabrafenib as a lea...

    journal_title：Bioorganic chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bioorg.2020.104508

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

    更新日期：2021-01-01 00:00:00

  • Discovery of a series of selective and cell permeable beta-secretase (BACE1) inhibitors by fragment linking with the assistance of STD-NMR.

    abstract：:Two β-secreatase (BACE1) inhibitors from natural products (cinnamic acid and flavone) were linked to furnish potent, cell permeable BACE1 inhibitors with noncompetitive mode of inhibition, with the assistance of saturated transfer difference (STD)-NMR technique. Some of these conjugates also exhibited selective BACE1 ...

    journal_title：Bioorganic chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bioorg.2019.103253

    authors： Fang WS,Sun DY,Yang S,Cheng C,Moschke K,Li T,Sun S,Lichtenthaler SF,Huang J,Wang Y

    更新日期：2019-11-01 00:00:00