The design and synthesis of a novel compound of berberine and baicalein that inhibits the efficacy of lipid accumulation in 3T3-L1 adipocytes.

Abstract:

:The combination of berberine and baicalein may have a better therapeutic effect against disease. To explore the combined effect of baicalein and berberine in the treatment of obesity, we designed and synthesized a hybrid compound, and its biological activities were evaluated in 3T3-L1 adipocytes. The structures of the berberine-baicalein (BBS) compounds were confirmed by 1H NMR, 13C NMR, ultraviolet spectroscopy and high resolution mass spectrometry (HRMS). The present study showed that the IC50 values of the inhibitory effects of baicalein, berberine and BBS against 3T3-L1 cells were 29.81±0.90, 21.84±1.67 and 9.42±0.60µM, respectively. The expression of mRNAs related to lipolysis and lipogenesis were examined by quantitative real-time PCR. The results showed that BBS could up-regulate the expression of the Atgl gene and down-regulate the mRNA expression of Srebp-1c, Fasn, Scd1, and Acc in 3T3-L1 adipocytes. These results indicate that BBS may have a stronger effect than baicalein and berberine on the viability of 3T3-L1 preadipocytes. In addition, BBS may have therapeutic effects and pharmacological activities against obesity. This "medicine couple" may be beneficial for studies of traditional Chinese medicine.

journal_name

Bioorg Med Chem

authors

Hao M,Li Y,Liu L,Yuan X,Gao Y,Guan Z,Li W

doi

10.1016/j.bmc.2017.08.013

subject

Has Abstract

pub_date

2017-10-15 00:00:00

pages

5506-5512

issue

20

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(17)31336-6

journal_volume

25

pub_type

杂志文章
  • Development of a potent 2-oxoamide inhibitor of secreted phospholipase A2 guided by molecular docking calculations and molecular dynamics simulations.

    abstract::Inhibition of group IIA secreted phospholipase A2 (GIIA sPLA2) has been an important objective for medicinal chemists. We have previously shown that inhibitors incorporating the 2-oxoamide functionality may inhibit human and mouse GIIA sPLA2s. Herein, the development of new potent inhibitors by molecular docking calcu...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2016.02.040

    authors: Vasilakaki S,Barbayianni E,Leonis G,Papadopoulos MG,Mavromoustakos T,Gelb MH,Kokotos G

    更新日期:2016-04-15 00:00:00

  • Design, synthesis, and biological evaluation of novel 4-oxobenzo[d]1,2,3-triazin-benzylpyridinum derivatives as potent anti-Alzheimer agents.

    abstract::Novel 4-oxobenzo[d]1,2,3-triazin derivatives bearing pyridinium moiety 6a-q were synthesized and screened against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Most of the synthesized compounds showed good inhibitory activity against AChE. Among the synthesized compounds, the compound 6j exhibited the...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2019.05.023

    authors: Hosseini F,Ramazani A,Mohammadi-Khanaposhtani M,Barazandeh Tehrani M,Nadri H,Larijani B,Mahdavi M

    更新日期:2019-07-01 00:00:00

  • Dual inhibitors of inosine monophosphate dehydrogenase and histone deacetylase based on a cinnamic hydroxamic acid core structure.

    abstract::Small molecules that act on multiple biological targets have been proposed to combat the drug resistance commonly observed for cancer chemotherapy. By combining the structural features of known inhibitors of inosine monophosphate dehydrogense (IMPDH) and histone deacetylase (HDAC), dual inhibitors of IMPDH and HDAC ba...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2010.06.081

    authors: Chen L,Petrelli R,Gao G,Wilson DJ,McLean GT,Jayaram HN,Sham YY,Pankiewicz KW

    更新日期:2010-08-15 00:00:00

  • QSAR models for Daphnia toxicity of pesticides based on combinations of topological parameters of molecular structures.

    abstract::A topological parameter is defined as an integer value of a given local or global invariant of a molecular graph. We examined three types of local graph invariants, the vertex degrees (0EC), the extended connectivity of first order (1EC), and the numbers of paths of length two (P2), as elementary invariants for constr...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2005.11.060

    authors: Toropov AA,Benfenati E

    更新日期:2006-04-15 00:00:00

  • The tyrosinase inhibitory effects of isoxazolone derivatives with a (Z)-β-phenyl-α, β-unsaturated carbonyl scaffold.

    abstract::Thirteen (Z)-4-(substituted benzylidene)-3-phenylisoxazol-5(4H)-ones were designed to confirm the geometric effect of the double bond of the β-phenyl-α, β-unsaturated carbonyl scaffold on tyrosinase inhibitory activity. Compounds 1a-1m, which all possessed the (Z)-β-phenyl-α, β-unsaturated carbonyl scaffold, were synt...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2018.05.047

    authors: Kim SJ,Yang J,Lee S,Park C,Kang D,Akter J,Ullah S,Kim YJ,Chun P,Moon HR

    更新日期:2018-08-07 00:00:00

  • Synthesis, topoisomerase I and II inhibitory activity, cytotoxicity, and structure-activity relationship study of 2-phenyl- or hydroxylated 2-phenyl-4-aryl-5H-indeno[1,2-b]pyridines.

    abstract::A series of novel twenty-eight rigid 2-phenyl- or hydroxylated 2-phenyl-4-aryl-5H-indeno[1,2-b]pyridines were synthesized and evaluated for their topoisomerase inhibitory activity as well as their cytotoxicity against several human cancer cell lines. Generally, hydroxylated compounds (16-18, 22-25, and 29-31) containi...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2015.04.031

    authors: Kadayat TM,Song C,Shin S,Magar TB,Bist G,Shrestha A,Thapa P,Na Y,Kwon Y,Lee ES

    更新日期:2015-07-01 00:00:00

  • 6-Hydrophobic aromatic substituent pyrimethamine analogues as potential antimalarials for pyrimethamine-resistant Plasmodium falciparum.

    abstract::The series of des-Cl (unsubstituted) and m-Cl phenyl analogues of PYR with various flexible 6-substituents were synthesized and studied for the binding affinities with highly resistant quadruple mutant (QM) DHFR. The derivatives carrying 4 atoms linker with a terminal carboxyl substituted on the aromatic ring exhibite...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2019.115158

    authors: Saepua S,Sadorn K,Vanichtanankul J,Anukunwithaya T,Rattanajak R,Vitsupakorn D,Kamchonwongpaisan S,Yuthavong Y,Thongpanchang C

    更新日期:2019-12-15 00:00:00

  • N-phenethyl and N-naphthylmethyl isatins and analogues as in vitro cytotoxic agents.

    abstract::A range of N-phenethyl, N-phenacyl, and N-(1- and 2-naphthylmethyl) derivatives of 5,7-dibromoisatin 2 were prepared by N-alkylation reactions. Their activity against human monocyte-like histiocytic lymphoma (U937), leukemia (Jurkat), and breast carcinoma (MDA-MB-231) cell lines was assessed. The results allowed furth...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2007.12.026

    authors: Matesic L,Locke JM,Bremner JB,Pyne SG,Skropeta D,Ranson M,Vine KL

    更新日期:2008-03-15 00:00:00

  • 5-demethylovalicin, as a methionine aminopeptidase-2 inhibitor produced by Chrysosporium.

    abstract::5-Demethylovalicin was isolated from the fermentation broth Chrysosporium lucknowense and the structure was identified by spectroscopic methods. 5-Demethylovalicin inhibited the recombinant human MetAP-2 (IC(50)=17.7 nM) and the growth of human umbilical vein endothelial cells (HUVEC; IC(50)=100 nM) in cell proliferat...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/s0968-0896(01)00268-1

    authors: Son KH,Kwon JY,Jeong HW,Kim HK,Kim CJ,Chang YH,Choi JD,Kwon BM

    更新日期:2002-01-01 00:00:00

  • Structure-activity studies of sulfate transfer: the hydrolysis and aminolysis of 3'-phosphoadenosine 5'-phosphosulfate (PAPS).

    abstract::The pH-rate profile for the hydrolysis of 3'-phosphoadenosine 5'-phosphosulfate (PAPS) in aqueous solution has been measured. Comparison with other data suggests that hydrolysis occurs by almost complete unimolecular elimination of sulfur trioxide, with weak involvement of a molecule of water in the transition state. ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/0968-0896(95)00015-9

    authors: Bedford CT,Kirby AJ,Logan CJ,Drummond JN

    更新日期:1995-02-01 00:00:00

  • Discovery of melanin-concentrating hormone receptor R1 antagonists using high-throughput synthesis.

    abstract::A structure-activity study on benzylpiperidine 1 was accomplished by utilizing high-throughput synthesis. Three focused libraries were designed and synthesized to quickly develop SAR. Further optimization led to the discovery of compound 2, an MCH receptor R1 antagonist with over 400-fold improvement in biological act...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2004.11.046

    authors: Su J,McKittrick BA,Tang H,Czarniecki M,Greenlee WJ,Hawes BE,O'Neill K

    更新日期:2005-03-01 00:00:00

  • Novel structure-activity relationships and selectivity profiling of cage dimeric 1,4-dihydropyridines as multidrug resistance (MDR) modulators.

    abstract::Synthesized series of cage dimeric 1,4-dihydropyridines have been systematically evaluated as MDR modulators in in vitro assays to investigate structure-dependent selectivity properties of inhibiting most cancer-relevant efflux pump proteins. Structure-activity relationships of each P-glycoprotein (P-gp) and multidrug...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2010.06.004

    authors: Coburger C,Wollmann J,Krug M,Baumert C,Seifert M,Molnár J,Lage H,Hilgeroth A

    更新日期:2010-07-15 00:00:00

  • Cloning, characterization and anion inhibition studies of a new γ-carbonic anhydrase from the Antarctic bacterium Pseudoalteromonas haloplanktis.

    abstract::A new γ-class carbonic anhydrase (CA, EC 4.2.1.1) was cloned, purified and characterized from the Antarctic bacterium Pseudoalteromonas haloplanktis, PhaCAγ. The enzyme has a medium-low catalytic activity for the physiologic reaction of CO2 hydration to bicarbonate and protons, with a kcat of 1.4×10(5)s(-1) and a kcat...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2015.06.021

    authors: De Luca V,Vullo D,Del Prete S,Carginale V,Scozzafava A,Osman SM,AlOthman Z,Supuran CT,Capasso C

    更新日期:2015-08-01 00:00:00

  • Inhibition studies of the β-carbonic anhydrases from the bacterial pathogen Salmonella enterica serovar Typhimurium with sulfonamides and sulfamates.

    abstract::The two β-carbonic anhydrases (CAs, EC 4.2.1.1) from the bacterial pathogen Salmonella enterica serovar Typhimurium, stCA 1 and stCA 2, were investigated for their inhibition with a large panel of sulfonamides and sulfamates. Unlike inorganic anions, which are weak, millimolar inhibitors of the two enzymes [Vullo et a...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2011.06.038

    authors: Nishimori I,Minakuchi T,Vullo D,Scozzafava A,Supuran CT

    更新日期:2011-08-15 00:00:00

  • A novel assay revealed that ribonucleotide reductase is functionally important for interstrand DNA crosslink repair.

    abstract::Cells have evolved complex biochemical pathways for DNA interstrand crosslink (ICL) removal. Despite the chemotherapeutic importance of ICL repair, there have been few attempts to identify which mechanistic DNA repair inhibitor actually inhibits ICL repair. To identify such compounds, a new and robust ICL repair assay...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2015.09.045

    authors: Fujii N,Evison BJ,Actis ML,Inoue A

    更新日期:2015-11-01 00:00:00

  • Design, synthesis and biological evaluation of (E)-3,4-dihydroxystyryl 4-acylaminophenethyl sulfone, sulfoxide derivatives as dual inhibitors of HIV-1 CCR5 and integrase.

    abstract::Aiming at the limited effectiveness of current clinical therapeutic effect of AIDS, novel series of compounds bearing (E)-3,4-dihydroxystyryl sulfone (or sulfoxide) and anilide fragments were designed and synthesized as dual inhibitors of HIV-1 CCR5/IN. The biological results indicated that several target compounds sh...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2016.12.035

    authors: Sun Y,Xu W,Fan N,Sun X,Ning X,Ma L,Liu J,Wang X

    更新日期:2017-02-01 00:00:00

  • QSAR of 1,4-benzoxazin-3-one antimicrobials and their drug design perspectives.

    abstract::Synthetic derivatives of 1,4-benzoxazin-3-ones have been shown to possess promising antimicrobial activity, whereas their natural counterparts were found lacking in this respect. In this work, quantitative structure-activity relationships (QSAR) of natural and synthetic 1,4-benzoxazin-3-ones as antimicrobials were est...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2018.11.016

    authors: de Bruijn WJC,Hageman JA,Araya-Cloutier C,Gruppen H,Vincken JP

    更新日期:2018-12-15 00:00:00

  • QSAR treatment of drugs transfer into human breast milk.

    abstract::A satisfactory model is developed using CODESSA PRO for the correlation and prediction of milk to plasma concentration ratios (M/P ratio) for diverse pharmaceuticals. A set of experimentally derived M/P ratio values were collected from the literature for 115 widely used pharmaceuticals. The experimental logarithmic M/...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2004.12.015

    authors: Katritzky AR,Dobchev DA,Hür E,Fara DC,Karelson M

    更新日期:2005-03-01 00:00:00

  • Synthesis of cryptolepine analogues as potential bioreducible anticancer agents.

    abstract::A series of 10 novel nitro-analogues of cryptolepine (1) has been synthesised and these compounds were evaluated for their in-vitro cytotoxic properties as well as their potential for reductive activation by the cytosolic reductase enzymes NQO1 and NQO2. Molecular modelling studies suggest that cryptolepine is able to...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2007.06.062

    authors: Seville S,Phillips RM,Shnyder SD,Wright CW

    更新日期:2007-10-01 00:00:00

  • Syntheses and pharmacological characterization of novel thiazole derivatives as potential mGluR5 PET ligands.

    abstract::Four novel thiazole containing ABP688 derivatives were synthesized and evaluated for their binding affinity towards the metabotropic glutamate receptor subtype 5 (mGluR5). (E)-3-((2-(Fluoromethyl)thiazol-4-yl)ethynyl)cyclohex-2-enone O-methyl oxime (FTECMO), the ligand with the highest binding affinity (K(i)=5.5+/-1.1...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2010.06.070

    authors: Baumann CA,Mu L,Wertli N,Krämer SD,Honer M,Schubiger PA,Ametamey SM

    更新日期:2010-08-15 00:00:00

  • Structure-activity relationships of antitubercular salicylanilides consistent with disruption of the proton gradient via proton shuttling.

    abstract::A series of salicylanilides was synthesized based on a high-throughput screening hit against Mycobacterium tuberculosis. A free phenolic hydroxyl on the salicylic acid moeity is required for activity, and the structure-activity relationship of the aniline ring is largely driven by the presence of electron withdrawing ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2012.10.056

    authors: Lee IY,Gruber TD,Samuels A,Yun M,Nam B,Kang M,Crowley K,Winterroth B,Boshoff HI,Barry CE 3rd

    更新日期:2013-01-01 00:00:00

  • Design and synthesis of marine fungal phthalide derivatives as PPAR-γ agonists.

    abstract::On the basis of a marine fungal phthalide (paecilocin A) skeleton, we synthesized 20 analogs and evaluated them for peroxisome proliferator-activated receptor gamma (PPAR-γ) binding and activation. Among these analogs, 6 and 7 had significant PPAR-γ binding activity, and 7 showed further PPAR-γ activation in rat liver...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2012.06.039

    authors: Xiao B,Yin J,Park M,Liu J,Li JL,Kim EL,Hong J,Chung HY,Jung JH

    更新日期:2012-08-15 00:00:00

  • Luciferase-based HMG-CoA reductase degradation assay for activity and selectivity profiling of oxy(lano)sterols.

    abstract::HMG-CoA reductase (HMGCR) is the rate-limiting enzyme in the cholesterol biosynthetic pathway, and is the target of cholesterol-lowering drugs, statins. Previous studies have demonstrated that the enzyme activity is regulated by sterol-induced degradation in addition to transcriptional regulation through sterol-regula...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2019.115298

    authors: Sagimori I,Yoshioka H,Hashimoto Y,Ohgane K

    更新日期:2020-02-01 00:00:00

  • Structure-based discovery of small molecule hepsin and HGFA protease inhibitors: Evaluation of potency and selectivity derived from distinct binding pockets.

    abstract::Hepatocyte growth factor activator (HGFA), matriptase and hepsin are all S1 trypsin-like serine endopeptidases. HGFA is a plasma protease while hepsin and matriptase are type II transmembrane proteases (TTSPs). Upregulated expression and activity of all three proteases is associated with aberrant cancer cell signaling...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2015.03.072

    authors: Franco FM,Jones DE,Harris PK,Han Z,Wildman SA,Jarvis CM,Janetka JW

    更新日期:2015-05-15 00:00:00

  • Synthesis and biological evaluation of N-(carbobenzyloxy)-l-phenylalanine and N-(carbobenzyloxy)-l-aspartic acid-β-benzyl ester derivatives as potent topoisomerase IIα inhibitors.

    abstract::A new series of thirteen N-(carbobenzyloxy)-l-phenylalanine and N-(carbobenzyloxy)-l-aspartic acid-β-benzyl ester compounds were synthesized and evaluated for antiproliferative activity against four different human cancer cell lines: cervical cancer (HeLa), lung cancer (A549), gastric cancer (MGC-803) and breast cance...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2017.03.065

    authors: Han X,Zhong Y,Zhou G,Qi H,Li S,Ding Q,Liu Z,Song Y,Qiao X

    更新日期:2017-06-15 00:00:00

  • Reactivity of dimethyl fumarate and methylhydrogen fumarate towards glutathione and N-acetyl-L-cysteine--preparation of S-substituted thiosuccinic acid esters.

    abstract::Dimethyl fumarate (DMF) is used successfully to treat psoriasis. In spite of its proven clinical efficacy, the mode of metabolism and the pharmacodynamics of DMF are still not completely understood. Some previous studies have indicated that orally applied DMF for a considerable part is quickly hydrolysed to methylhydr...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2006.09.053

    authors: Schmidt TJ,Ak M,Mrowietz U

    更新日期:2007-01-01 00:00:00

  • Total synthesis and a systematic structure-activity relationship study of WAP-8294A2.

    abstract::WAP-8294A2 is a cyclic peptide antibiotic with novel structure and excellent activity against Gram-positive pathogens. Herein, we report the total synthesis of complex macrocyclic peptide WAP-8294A2 (W1), ent-analogue W2, deoxy analogue W3 and de-methyl analogue W4 using a solid-phase synthetic route followed by a fin...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2020.115677

    authors: Chen D,Tian L,Po KHL,Chen S,Li X

    更新日期:2020-09-15 00:00:00

  • Structure-activity relationship and biological property of cortistatins, anti-angiogenic spongean steroidal alkaloids.

    abstract::Previously, bioassay-guided separation led us to isolate eleven novel steroidal alkaloids named cortistatins from the marine sponge Corticium simplex. These cortistatins were classified into three types based on the chemical structure of the side chain part, that is, isoquinoline, N-methyl piperidine or 3-methylpyridi...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2007.08.017

    authors: Aoki S,Watanabe Y,Tanabe D,Arai M,Suna H,Miyamoto K,Tsujibo H,Tsujikawa K,Yamamoto H,Kobayashi M

    更新日期:2007-11-01 00:00:00

  • Concise syntheses of arabinogalactans with beta-(1-->6)-linked galactopyranose backbones and alpha-(1-->3)- and alpha-(1-->2)-linked arabinofuranose side chains.

    abstract::4-methoxyphenyl glycosides of 2,3''-bis-alpha-L-arabinofuranosyl branched beta-D-(1-->6)-linked galactopyranosyl tetraose (16), 3',2''''-bis-alpha-L-arabinofuranosyl branched beta-D-(1-->6)-linked galactopyranosyl hexaose (27), and a twentyose (42) consisting of beta-(1-->6)-linked D-galactopyranosyl pentadecaoligosac...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2004.10.035

    authors: Li A,Kong F

    更新日期:2005-02-01 00:00:00

  • Enhancing effect of indirubin derivatives on 1,25-dihydroxyvitamin D3- and all-trans retinoic acid-induced differentiation of HL-60 leukemia cells.

    abstract::The induction of differentiation represents a new and promising approach to cancer therapy, well illustrated by the treatment of acute promyelocytic leukemia (APL) with 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] or all-trans retinoic acid (ATRA). Using combinations of low, nontoxic concentrations of either 1,25-(OH)2D3 o...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2006.05.044

    authors: Kim SH,Kim SW,Choi SJ,Kim YC,Kim TS

    更新日期:2006-10-01 00:00:00