Design, Synthesis, and Cytotoxic Analysis of Novel Hederagenin⁻Pyrazine Derivatives Based on Partial Least Squares Discriminant Analysis.


:Hederagenin (He) is a novel triterpene template for the development of new antitumor compounds. In this study, 26 new He⁻pyrazine derivatives were synthetized in an attempt to develop potent antitumor agents; they were screened for in vitro cytotoxicity against tumor and non-tumor cell lines. The majority of these derivatives showed much stronger cytotoxic activity than He. Remarkably, the most potent was compound 9 (half maximal inhibitory concentration (IC50) was 3.45 ± 0.59 μM), which exhibited similar antitumor activities against A549 (human non-small-cell lung cancer) as the positive drug cisplatin (DDP; IC50 was 3.85 ± 0.63 μM), while it showed lower cytotoxicity on H9c2 (murine heart myoblast; IC50 was 16.69 ± 0.12 μM) cell lines. Compound 9 could induce the early apoptosis and evoke cell-cycle arrest at the synthesis (S) phase of A549 cells. Impressively, we innovatively introduced the method of cluster analysis modeled as partial least squares discriminant analysis (PLS-DA) into the structure⁻activity relationship (SAR) evaluation, and SAR confirmed that pyrazine had a profound effect on the antitumor activity of He. The present studies highlight the importance of pyrazine derivatives of He in the discovery and development of novel antitumor agents.


Int J Mol Sci


Fang K,Zhang XH,Han YT,Wu GR,Cai DS,Xue NN,Guo WB,Yang YQ,Chen M,Zhang XY,Wang H,Ma T,Wang PL,Lei HM




Has Abstract


2018-09-30 00:00:00










  • Characterization of Carbonic Anhydrase In Vivo Using Magnetic Resonance Spectroscopy.

    abstract::Carbonic anhydrase is a ubiquitous metalloenzyme that catalyzes the reversible interconversion of CO2/HCO3-. Equilibrium of these species is maintained by the action of carbonic anhydrase. Recent advances in magnetic resonance spectroscopy have allowed, for the first time, in vivo characterization of carbonic anhydras...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审


    authors: Tomar JS,Shen J

    更新日期:2020-04-01 00:00:00

  • GaAs-Based InPBi Quantum Dots for High Efficiency Super-Luminescence Diodes.

    abstract::InPBi exhibits broad and strong photoluminescence at room temperature, and is a potential candidate for fabricating super-luminescence diodes applied in optical coherence tomography. In this paper, the strained InPBi quantum dot (QD) embedded in the AlGaAs barrier on a GaAs platform is proposed to enhance the light em...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Zhang L,Song Y,Gong Q

    更新日期:2019-11-28 00:00:00

  • Generation of Organized Porcine Testicular Organoids in Solubilized Hydrogels from Decellularized Extracellular Matrix.

    abstract::Cryopreservation of immature testicular tissue (ITT) prior to chemo/radiotherapy is now ethically accepted and is currently the only way to preserve fertility of prepubertal boys about to undergo cancer therapies. So far, three-dimensional culture of testicular cells isolated from prepubertal human testicular tissue w...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Vermeulen M,Del Vento F,Kanbar M,Pyr Dit Ruys S,Vertommen D,Poels J,Wyns C

    更新日期:2019-11-03 00:00:00

  • Matrix Metalloproteinase Response of Dendritic Cell, Gingival Epithelial Keratinocyte, and T-Cell Transwell Co-Cultures Treated with Porphyromonas gingivalis Hemagglutinin-B.

    abstract::Matrix metalloproteinases (MMPs) are enzymes involved in periodontal tissue destruction. Hemagglutinin B (HagB) from the periodontal pathogen Porphyromonas gingivalis induces an elevated MMP response in dendritic cells, but responses from cultures of single-cell types do not reflect the local tissue environment. The o...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Bates AM,Fischer CL,Abhyankar VP,Johnson GK,Guthmiller JM,Progulske-Fox A,Brogden KA

    更新日期:2018-12-07 00:00:00

  • Identification of RNA-Binding Proteins as Targetable Putative Oncogenes in Neuroblastoma.

    abstract::Neuroblastoma is a common childhood cancer with almost a third of those affected still dying, thus new therapeutic strategies need to be explored. Current experimental therapies focus mostly on inhibiting oncogenic transcription factor signalling. Although LIN28B, DICER and other RNA-binding proteins (RBPs) have repor...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Bell JL,Hagemann S,Holien JK,Liu T,Nagy Z,Schulte JH,Misiak D,Hüttelmaier S

    更新日期:2020-07-19 00:00:00

  • The Role of Sirtuins in Kidney Diseases.

    abstract::Sirtuins (SIRTs) are class III histone deacetylases (HDACs) that play important roles in aging and a wide range of cellular functions. Sirtuins are crucial to numerous biological processes, including proliferation, DNA repair, mitochondrial energy homeostasis, and antioxidant activity. Mammals have seven different sir...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审


    authors: Hong YA,Kim JE,Jo M,Ko GJ

    更新日期:2020-09-12 00:00:00

  • The Protective Effect of Chlorogenic Acid on Vascular Senescence via the Nrf2/HO-1 Pathway.

    abstract::The world faces the serious problem of aging. In this study, we aimed to investigate the effect of chlorogenic acid (CGA) on vascular senescence. C57/BL6 female mice that were 14 ± 3 months old were infused with either Angiotensin II (AngII) or saline subcutaneously for two weeks. These mice were administered CGA of 2...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Hada Y,Uchida HA,Otaka N,Onishi Y,Okamoto S,Nishiwaki M,Takemoto R,Takeuchi H,Wada J

    更新日期:2020-06-25 00:00:00

  • Genome-Wide Analysis, Expression Profile, and Characterization of the Acid Invertase Gene Family in Pepper.

    abstract::Catalytic decomposition of sucrose by acid invertases (AINVs) under acidic conditions plays an important role in the development of sink organs in plants. To reveal the function of AINVs in the development of pepper fruits, nine AINV genes of pepper were identified. Protein sequencing and phylogenetic analysis reveale...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Shen LB,Qin YL,Qi ZQ,Niu Y,Liu ZJ,Liu WX,He H,Cao ZM,Yang Y

    更新日期:2018-12-20 00:00:00

  • In Situ β-Glucan Fortification of Cereal-Based Matrices by Pediococcus parvulus 2.6: Technological Aspects and Prebiotic Potential.

    abstract::Bacterial exopolysaccharides produced by lactic acid bacteria are of increasing interest in the food industry, since they might enhance the technological and functional properties of some edible matrices. In this work, Pediococcus parvulus 2.6, which produces an O2-substituted (1,3)-β-d-glucan exopolysaccharide only s...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Pérez-Ramos A,Mohedano ML,López P,Spano G,Fiocco D,Russo P,Capozzi V

    更新日期:2017-07-21 00:00:00

  • Influence of Cationic meso-Substituted Porphyrins on the Antimicrobial Photodynamic Efficacy and Cell Membrane Interaction in Escherichia coli.

    abstract::Photodynamic inactivation (PDI) is a non-antibiotic option for the treatment of infectious diseases. Although Gram-positive bacteria have been shown to be highly susceptible to PDI, the inactivation of Gram-negative bacteria has been more challenging due to the impermeability properties of the outer membrane. In the p...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Hurst AN,Scarbrough B,Saleh R,Hovey J,Ari F,Goyal S,Chi RJ,Troutman JM,Vivero-Escoto JL

    更新日期:2019-01-01 00:00:00

  • How can plant DNA viruses evade siRNA-directed DNA methylation and silencing?

    abstract::Plants infected with DNA viruses produce massive quantities of virus-derived, 24-nucleotide short interfering RNAs (siRNAs), which can potentially direct viral DNA methylation and transcriptional silencing. However, growing evidence indicates that the circular double-stranded DNA accumulating in the nucleus for Pol II...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审


    authors: Pooggin MM

    更新日期:2013-07-24 00:00:00

  • Overexpression of ABCB1 Transporter Confers Resistance to mTOR Inhibitor WYE-354 in Cancer Cells.

    abstract::The overexpressing ABCB1 transporter is one of the key factors leading to multidrug resistance (MDR). Thus, many ABCB1 inhibitors have been found to be able to overcome ABCB1-mediated MDR. However, some inhibitors also work as a substrate of ABCB1, which indicates that in order to achieve an effective reversal dosage,...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Wang J,Yang DH,Yang Y,Wang JQ,Cai CY,Lei ZN,Teng QX,Wu ZX,Zhao L,Chen ZS

    更新日期:2020-02-19 00:00:00

  • Immunomodulation Induced by Stem Cell Mobilization and Harvesting in Healthy Donors: Increased Systemic Osteopontin Levels after Treatment with Granulocyte Colony-Stimulating Factor.

    abstract::Peripheral blood stem cells from healthy donors mobilized by granulocyte colony-stimulating factor (G-CSF) and harvested by leukapheresis are commonly used for allogeneic stem cell transplantation. The frequency of severe graft versus host disease is similar for patients receiving peripheral blood and bone marrow allo...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Melve GK,Ersvaer E,Akkök ÇA,Ahmed AB,Kristoffersen EK,Hervig T,Bruserud Ø

    更新日期:2016-07-19 00:00:00

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    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Jin L,Guo T,Li Z,Lei Z,Li H,Mao Y,Wang X,Zhou N,Zhang Y,Hu R,Zhang X,Niu G,Irwin DM,Tan H

    更新日期:2015-04-02 00:00:00

  • GI inflammation Increases Sodium-Glucose Cotransporter Sglt1.

    abstract::A correlation between gastrointestinal (GI) inflammation and gut hormones has reported that inflammatory stimuli including bacterial endotoxins, lipopolysaccharides (LPS), TNFα, IL-1β, and IL-6 induces high levels of incretin hormone leading to glucose dysregulation. Although incretin hormones are immediately secreted...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Park J,Lee IS,Kim KH,Kim Y,An EJ,Jang HJ

    更新日期:2019-05-23 00:00:00

  • Physicochemical and Antimicrobial Characterization of Beeswax-Starch Food-Grade Nanoemulsions Incorporating Natural Antimicrobials.

    abstract::Nanoemulsions are feasible delivery systems of lipophilic compounds, showing potential as edible coatings with enhanced functional properties. The aim of this work was to study the effect of emulsifier type (stearic acid (SA), Tween 80 (T80) or Tween 80/Span 60 (T80/S60)) and emulsification process (homogenization, ul...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Arredondo-Ochoa T,García-Almendárez BE,Escamilla-García M,Martín-Belloso O,Rossi-Márquez G,Medina-Torres L,Regalado-González C

    更新日期:2017-12-15 00:00:00

  • Spent Brewer's Yeast as a Source of Insoluble β-Glucans.

    abstract::In the brewing process, the consumption of resources and the amount of waste generated are high and due to a lot of organic compounds in waste-water, the capacity of natural regeneration of the environment is exceeded. Residual yeast, the second by-product of brewing is considered to have an important chemical composi...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审


    authors: Avramia I,Amariei S

    更新日期:2021-01-15 00:00:00

  • Confocal Spectroscopy to Study Dimerization, Oligomerization and Aggregation of Proteins: A Practical Guide.

    abstract::Protein self-association is a key feature that can modulate the physiological role of proteins or lead to deleterious effects when uncontrolled. Protein oligomerization is a simple way to modify the activity of a protein, as the modulation of binding interfaces allows for self-activation or inhibition, or variation in...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审


    authors: Gambin Y,Polinkovsky M,Francois B,Giles N,Bhumkar A,Sierecki E

    更新日期:2016-04-30 00:00:00

  • Do Atypical Antipsychotics Have Antisuicidal Effects? A Hypothesis-Generating Overview.

    abstract::Modern antipsychotic drugs are employed increasingly in the treatment of mood disorders as well as psychoses, stimulating interest in their possible contributions to altering suicidal risk. Clozapine remains the only treatment with an FDA-recognized indication for reducing suicidal risk (in schizophrenia). We carried ...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审


    authors: Pompili M,Baldessarini RJ,Forte A,Erbuto D,Serafini G,Fiorillo A,Amore M,Girardi P

    更新日期:2016-10-11 00:00:00

  • Structural Identification of Antibacterial Lipids from Amazonian Palm Tree Endophytes through the Molecular Network Approach.

    abstract::A library of 197 endophytic fungi and bacteria isolated from the Amazonian palm tree Astrocaryum sciophilum was extracted and screened for antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). Four out of five antibacterial ethyl acetate extracts were also cytotoxic for the MRC-5 cells lin...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Barthélemy M,Elie N,Pellissier L,Wolfender JL,Stien D,Touboul D,Eparvier V

    更新日期:2019-04-24 00:00:00

  • Zinc as a Signal to Stimulate Red Blood Cell Formation in Fish.

    abstract::The common carp can tolerate extremely low oxygen levels. These fish store zinc in a specific zinc-binding protein presented in digestive tract tissues, and under low oxygen, the stored zinc is released and used as a signal to stimulate erythropoiesis (red blood cell formation). To determine whether the environmental ...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Chen YH,Shiu JR,Ho CL,Jeng SS

    更新日期:2017-01-11 00:00:00

  • Stem cell tracking by nanotechnologies.

    abstract::Advances in stem cell research have provided important understanding of the cell biology and offered great promise for developing new strategies for tissue regeneration. The beneficial effects of stem cell therapy depend also by the development of new approachs for the track of stem cells in living subjects over time ...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审


    authors: Villa C,Erratico S,Razini P,Fiori F,Rustichelli F,Torrente Y,Belicchi M

    更新日期:2010-03-12 00:00:00

  • Development and Characterisation of a Human Chronic Skin Wound Cell Line-Towards an Alternative for Animal Experimentation.

    abstract::Background: Chronic skin wounds are a growing financial burden for healthcare providers, causing discomfort/immobility to patients. Whilst animal chronic wound models have been developed to allow for mechanistic studies and to develop/test potential therapies, such systems are not good representations of the human chr...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Caley M,Wall IB,Peake M,Kipling D,Giles P,Thomas DW,Stephens P

    更新日期:2018-03-27 00:00:00

  • The inhibition of RANKL-induced osteoclastogenesis through the suppression of p38 signaling pathway by naringenin and attenuation of titanium-particle-induced osteolysis.

    abstract::The aim of this study was to assess the effect of naringenin on osteoclastogenesis and titanium particle-induced osteolysis. Osteolysis from wear-induced particles and aseptic loosening are the most frequent late complications of total joint arthroplasty leading to revision of the prosthesis. Osteolysis during aseptic...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Wang W,Wu C,Tian B,Liu X,Zhai Z,Qu X,Jiang C,Ouyang Z,Mao Y,Tang T,Qin A,Zhu Z

    更新日期:2014-11-28 00:00:00

  • Growth suppression of colorectal cancer by plant-derived multiple mAb CO17-1A × BR55 via inhibition of ERK1/2 phosphorylation.

    abstract::We have generated the transgenic Tabaco plants expressing multiple monoclonal antibody (mAb) CO7-1A × BR55 by cross-pollinating with mAb CO17-1A and mAb BR55. We have demonstrated the anti-cancer effect of plant-derived multiple mAb CO17-1A × BR55. We find that co-treatment of colorectal mAbs (anti-epithelial cellular...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Kwak DH,Moussavou G,Lee JH,Heo SY,Ko K,Hwang KA,Jekal SJ,Choo YK

    更新日期:2014-11-14 00:00:00

  • Integrative Analysis of Regulatory Module Reveals Associations of Microgravity with Dysfunctions of Multi-body Systems and Tumorigenesis.

    abstract::Previous studies have demonstrated that microgravity could lead to health risks. The investigation of the molecular mechanisms from the aspect of systems biology has not been performed yet. Here, we integratively analyzed transcriptional and post-transcriptional regulations based on gene and miRNA expression profiles ...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Yuan M,Liu H,Zhou S,Zhou X,Huang YE,Hou F,Jiang W

    更新日期:2020-10-14 00:00:00

  • High-Throughput RNA-Seq Data Analysis of the Single Nucleotide Polymorphisms (SNPs) and Zygomorphic Flower Development in Pea (Pisum sativum L.).

    abstract::Pea (Pisum sativum L.) is a model plant that has been used in classical genetics and organ development studies. However, its large and complex genome has hindered research investigations in pea. Here, we generated transcriptomes from different tissues or organs of three pea accessions using next-generation sequencing ...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Jiao K,Li X,Guo W,Su S,Luo D

    更新日期:2017-12-20 00:00:00

  • Role of Arginine Methylation in Alternative Polyadenylation of VEGFR-1 (Flt-1) pre-mRNA.

    abstract::Mature mRNA is generated by the 3' end cleavage and polyadenylation of its precursor pre-mRNA. Eukaryotic genes frequently have multiple polyadenylation sites, resulting in mRNA isoforms with different 3'-UTR lengths that often encode different C-terminal amino acid sequences. It is well-known that this form of post-t...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审


    authors: Ikeda T,Saito-Takatsuji H,Yoshitomi Y,Yonekura H

    更新日期:2020-09-04 00:00:00

  • Role of Hypoxia and Metabolism in the Development of Neointimal Hyperplasia in Arteriovenous Fistulas.

    abstract::For patients with end-stage renal disease requiring hemodialysis, their vascular access is both their lifeline and their Achilles heel. Despite being recommended as primary vascular access, the arteriovenous fistula (AVF) shows sub-optimal results, with about 50% of patients needing a revision during the year followin...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审


    authors: Sadaghianloo N,Contenti J,Dardik A,Mazure NM

    更新日期:2019-10-29 00:00:00

  • Listeria Meningitis Complicating Alemtuzumab Treatment in Multiple Sclerosis--Report of Two Cases.

    abstract::Alemtuzumab, a humanized monoclonal antibody targeting the surface molecule CD52, leads to a rapid depletion of immune cells in the innate and adaptive immune system. In phase 2 and 3 trials in multiple sclerosis (MS), infections have been reported more frequently in alemtuzumab than in interferon beta treated patient...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Rau D,Lang M,Harth A,Naumann M,Weber F,Tumani H,Bayas A

    更新日期:2015-06-29 00:00:00