Design, Synthesis and in vivo Evaluation of Novel C-Aryl Glucosides as Potent Sodium-Dependent Glucose Cotransporters Inhibitors for the Treatment of Diabetes.

Abstract:

:A series of novel C-aryl glucosides with substituents at the 3'-position or cyclization at 3', 4'-positions of the distal aryl ring were designed and synthesized, which might decrease the oxidative metabolism of dapagliflozin. Preliminary evaluation for hypoglycemic effect and the risk of hypoglycemia were carried out both in normal and in streptozotocin-induced diabetic mice. Among the synthesized compounds, compound 19a exerted potency-similarity with dapagliflozin and triggered the hypoglycemic effect in a dose-dependent manner. Besides, compound 19a, even at the high dose of 10 mg/kg, revealed a low risk of hypoglycemia. In further studies, 19a exhibited sustained antihyperglycemic effect without particular side-effects in 30-day chronic diabetic mice studies. Moreover, histological changes in the pancreas of diabetic mice indicated 19a might protect pancreatic β-cell from apoptosis by reducing the damage of glucotoxicity. All of these results demonstrated that compound 19a, with excellent in vivo pharmacological activity and safety profile, was considered to be a promising drug candidate for the treatment of diabetes mellitus.

journal_name

Chem Biol Drug Des

authors

Li Z,Wang X,Xu X,Qiu Q,Jiao L,Huang W,Qian H

doi

10.1111/cbdd.12547

subject

Has Abstract

pub_date

2015-10-01 00:00:00

pages

764-75

issue

4

eissn

1747-0277

issn

1747-0285

journal_volume

86

pub_type

杂志文章
  • Comprehensive analysis of single- and multi-target activity cliffs formed by currently available bioactive compounds.

    abstract::Activity cliffs are formed by structurally similar compounds having large potency differences. Their study is a focal point of SAR analysis. We present a first systematic survey of single- and multitarget activity cliffs contained in currently available bioactive compounds. Approximately 12% of all active compounds we...

    journal_title:Chemical biology & drug design

    pub_type: 杂志文章

    doi:10.1111/j.1747-0285.2011.01150.x

    authors: Wassermann AM,Dimova D,Bajorath J

    更新日期:2011-08-01 00:00:00

  • Synthesis, analytical analysis, and medicinal aspect of novel benzimidazoles and their metal complexes.

    abstract::Benzimidazole and their metal analogs that can act as multimodal agent and have non-peptidic CCK-B receptor antagonist were synthesized and characterized on the basis of spectroscopic techniques such as FT-IR, NMR, FAB-MS and also evaluated for biologic efficacy. The ligands showed binding to most of the organs, known...

    journal_title:Chemical biology & drug design

    pub_type: 杂志文章

    doi:10.1111/cbdd.12201

    authors: Agrawal S,Bhatnagar RR,Tiwari A,Srivastava R,Sharma U

    更新日期:2013-11-01 00:00:00

  • The N-terminal region of CXCL11 as structural template for CXCR3 molecular recognition: synthesis, conformational analysis, and binding studies.

    abstract::The chemokines and their receptors play a key role in immune and inflammatory responses by promoting recruitment and activation of different subpopulations of leukocytes. The membrane receptor CXCR3 binds three chemokines, CXCL9, CXCL10, and CXCL11, and its involvement is recognized in many inflammatory diseases and c...

    journal_title:Chemical biology & drug design

    pub_type: 杂志文章

    doi:10.1111/j.1747-0285.2012.01397.x

    authors: Palladino P,Portella L,Colonna G,Raucci R,Saviano G,Rossi F,Napolitano M,Scala S,Castello G,Costantini S

    更新日期:2012-08-01 00:00:00

  • Effect of FSH receptor-binding inhibitor-8 on FSH-mediated granulosa cell signaling and proliferation.

    abstract::Follicle-stimulating hormone is important for mammalian reproduction. It acts through specific receptors located on the plasma membrane of granulosa cells in ovaries and Sertoli cells in testes. The binding of follicle-stimulating hormone to its receptor activates intracytoplasmic signaling pathways leading to steroid...

    journal_title:Chemical biology & drug design

    pub_type: 杂志文章

    doi:10.1111/cbdd.12149

    authors: Navalakhe RM,Jagtap DD,Nayak SU,Nandedkar TD,Mahale SD

    更新日期:2013-08-01 00:00:00

  • PiViewer: An open-source tool for automated detection and display of π-π interactions.

    abstract::π-π interactions are common and important noncovalent interactions that contribute to biochemical molecular interactions, but the tools for the convenient 3D visualization of π-π interactions are lacking. We have developed an open-source and easy-to-use tool for the automated identification and display of π-π stacking...

    journal_title:Chemical biology & drug design

    pub_type: 信件

    doi:10.1111/cbdd.13340

    authors: Liu Y,Ao X,Wang Q,Wang J,Ge H

    更新日期:2018-10-01 00:00:00

  • In vitro evaluation of doxorubicin-incorporated magnetic albumin nanospheres.

    abstract::Magnetic albumin nanospheres that incorporate doxorubicin (M-DOX-BSA-NPs) were prepared previously by our research group to develop magnetically responsive drug carrier system. This nanocarrier was synthesized as a drug delivery system for targeted chemotherapy. In this work, cytotoxic effects of doxorubicin (DOX)-loa...

    journal_title:Chemical biology & drug design

    pub_type: 杂志文章

    doi:10.1111/cbdd.12300

    authors: Zeybek A,Şanlı-Mohamed G,Ak G,Yılmaz H,Şanlıer ŞH

    更新日期:2014-07-01 00:00:00

  • Current state of a dual behaviour of antimicrobial peptides-Therapeutic agents and promising delivery vectors.

    abstract::Micro-organism resistance is an important challenge in modern medicine due to the global uncontrolled use of antibiotics. Natural and synthetic antimicrobial peptides (AMPs) symbolize a new family of antibiotics, which have stimulated research and clinical interest as new therapeutic options for infections. They repre...

    journal_title:Chemical biology & drug design

    pub_type: 杂志文章,评审

    doi:10.1111/cbdd.13031

    authors: Piotrowska U,Sobczak M,Oledzka E

    更新日期:2017-12-01 00:00:00

  • Identification of allosteric PIF-pocket ligands for PDK1 using NMR-based fragment screening and 1H-15N TROSY experiments.

    abstract::Aberrant activation of the phosphoinositide 3-kinase pathway because of genetic mutations of essential signalling proteins has been associated with human diseases including cancer and diabetes. The pivotal role of 3-phosphoinositide-dependent kinase-1 in the PI3K signalling cascade has made it an attractive target for...

    journal_title:Chemical biology & drug design

    pub_type: 杂志文章

    doi:10.1111/j.1747-0285.2008.00768.x

    authors: Stockman BJ,Kothe M,Kohls D,Weibley L,Connolly BJ,Sheils AL,Cao Q,Cheng AC,Yang L,Kamath AV,Ding YH,Charlton ME

    更新日期:2009-02-01 00:00:00

  • Combined 1H-NMR and molecular dynamics studies on conformational behavior of a model heptapeptide, GRGDSPC.

    abstract::Among various strategies, the de novo design and in silico approaches are being used to develop the short peptides, models of modified peptides, and mimetics as clinically useful drugs with improved stability and bioavailability. The resulting models will help to isolate the factors behind the folded structure formati...

    journal_title:Chemical biology & drug design

    pub_type: 杂志文章

    doi:10.1111/cbdd.12346

    authors: Kulkarni AK,Ojha RP

    更新日期:2014-11-01 00:00:00

  • Site-specific free energy changes in proteins upon ligand binding by nuclear magnetic resonance: Ca2+ -displacement by Ln3+ in a Ca2+ -binding protein from Entamoeba histolytica.

    abstract::The study of protein-ligand interaction has been of a great interest in contemporary structural biology. The understanding of the nature of such interaction and determining the associated binding affinities are of utmost importance. Nuclear magnetic resonance has become a powerful tool in deriving information related ...

    journal_title:Chemical biology & drug design

    pub_type: 杂志文章

    doi:10.1111/j.1747-0285.2011.01090.x

    authors: Chandra K,Mustafi SM,Muthukumar S,Chary KV

    更新日期:2011-04-01 00:00:00

  • Design, synthesis, and bioactivities screening of a diaryl ketone-inspired pesticide molecular library as derived from natural products.

    abstract::Three natural products, 1,5-diphenylpentan-1-one, 1,5-diphenylpent-2-en-1-one, and 3-hydroxy-1,5-diphenylpentan-1-one, with good insecticidal activities were extracted from Stellera chamaejasme L. Based on their shared diaryl ketone moiety as 'pharmacophores', a series of diaryl ketones were synthesized and tested for...

    journal_title:Chemical biology & drug design

    pub_type: 杂志文章

    doi:10.1111/j.1747-0285.2011.01082.x

    authors: Zhang H,Jin H,Ji LZ,Tao K,Liu W,Zhao HY,Hou TP

    更新日期:2011-07-01 00:00:00

  • Structure-based identification of aporphines with selective 5-HT(2A) receptor-binding activity.

    abstract::Selective blockade of the serotonin 5-HT(2A) receptor is a useful therapeutic approach for a number of disorders, including schizophrenia, insomnia and ischaemic heart disease. A series of aporphines were docked into a homology model of the rat 5-HT(2A) receptor using AutoDock. Selected compounds with high in silico b...

    journal_title:Chemical biology & drug design

    pub_type: 杂志文章

    doi:10.1111/cbdd.12069

    authors: Munusamy V,Yap BK,Buckle MJ,Doughty SW,Chung LY

    更新日期:2013-02-01 00:00:00

  • N-(2,4)-dinitrophenyl-L-arginine Interacts with EphB4 and Functions as an EphB4 Kinase Modulator.

    abstract::The erythropoietin-producing hepatocellular carcinoma receptor B4 is a receptor tyrosine kinase whose expression is preserved in various malignancies, including colon, gastric, and breast carcinoma. Hepatocellular carcinoma receptor B4 presence in tumor cells and involvement in cancer suppression makes it a potential ...

    journal_title:Chemical biology & drug design

    pub_type: 杂志文章

    doi:10.1111/cbdd.12510

    authors: Kamstra RL,Freywald A,Floriano WB

    更新日期:2015-10-01 00:00:00

  • Pharmacophore and QSAR studies to design novel histone deacetylase 2 inhibitors.

    abstract::One pharmacophore model and three quantitative structure-activity relationship models were developed on a series of benzimidazole and imidazole inhibitors of histone deacetylase 2. The goodness of hit score value of the best pharmacophore model was 0.756, which indicated that it is reliable to be used for virtual scre...

    journal_title:Chemical biology & drug design

    pub_type: 杂志文章

    doi:10.1111/j.1747-0285.2012.01341.x

    authors: Xiang Y,Hou Z,Zhang Z

    更新日期:2012-05-01 00:00:00

  • In vitro antioxidant activity study of novel chromone derivatives.

    abstract::Forty-eight chromone derivatives were evaluated for their antioxidant activity using 2,2-diphenyl-1-picrylhydrazyl free radical scavenging assay, ferrous ions (Fe(2+) ) chelating activity test, total antioxidant activity test (Ferric thiocyanate and Thiobarbituric acid methods), and total reductive capability (potassi...

    journal_title:Chemical biology & drug design

    pub_type: 杂志文章

    doi:10.1111/j.1747-0285.2012.01368.x

    authors: Phosrithong N,Samee W,Nunthanavanit P,Ungwitayatorn J

    更新日期:2012-06-01 00:00:00

  • Genome-wide DNA methylation and transcriptome and proteome changes in Mycobacterium tuberculosis with para-aminosalicylic acid resistance.

    abstract::Previous studies have reported that genome-wide DNA methylation and differentially expressed genes and proteins are closely associated with drug resistance in Mycobacterium tuberculosis (M. tuberculosis). However, no reports have explored such associations in para-aminosalicylic acid (PAS)-resistant M. tuberculosis H3...

    journal_title:Chemical biology & drug design

    pub_type: 杂志文章

    doi:10.1111/cbdd.13625

    authors: Li HC,Chen T,Yu L,Guo HX,Chen L,Chen YH,Chen M,Zhao J,Yan HM,Zhou L,Wang W

    更新日期:2020-01-01 00:00:00

  • A forward chemical screen using zebrafish embryos with novel 2-substituted 2H-chromene derivatives.

    abstract::We synthesized 2-substituted 2H-chromene derivatives from salicylaldehyde using potassium vinylic borates in the presence of secondary amines. Our goal was to generate novel compounds that might modulate transforming growth factor-beta signaling, based on limited rational design. Potassium vinyl trifluoroborates react...

    journal_title:Chemical biology & drug design

    pub_type: 杂志文章

    doi:10.1111/j.1747-0285.2009.00782.x

    authors: Torregroza I,Evans T,Das BC

    更新日期:2009-03-01 00:00:00

  • Increased diversity of libraries from libraries: chemoinformatic analysis of bis-diazacyclic libraries.

    abstract::Combinatorial libraries continue to play a key role in drug discovery. To increase structural diversity, several experimental methods have been developed. However, limited efforts have been performed so far to quantify the diversity of the broadly used diversity-oriented synthetic libraries. Herein, we report a compre...

    journal_title:Chemical biology & drug design

    pub_type: 杂志文章

    doi:10.1111/j.1747-0285.2011.01100.x

    authors: López-Vallejo F,Nefzi A,Bender A,Owen JR,Nabney IT,Houghten RA,Medina-Franco JL

    更新日期:2011-05-01 00:00:00

  • Synthesis and evaluation of thiouracil derivatives as dipeptidyl peptidase IV inhibitors.

    abstract::A series of thiouracil derivatives were designed, synthesized and screened for in vitro inhibition of dipeptidyl peptidase IV. The SAR study indicated the influence of substituted chemical modifications on thiouracil scaffold. Compounds 8 (IC(50) = 0.32 μM), 9 (IC(50) = 0.29 μM), and 12 (IC(50) = 0.25 μM) showed excel...

    journal_title:Chemical biology & drug design

    pub_type: 杂志文章

    doi:10.1111/cbdd.12070

    authors: Sharma M,Singh D,Gupta M

    更新日期:2013-02-01 00:00:00

  • A natural language processing approach based on embedding deep learning from heterogeneous compounds for quantitative structure-activity relationship modeling.

    abstract::Over the past decade, rapid development in biological and chemical technologies such as high-throughput screening, parallel synthesis, has been significantly increased the amount of data, which requires the creation and the integration of new analytical methods, especially deep learning models. Recently, there is an i...

    journal_title:Chemical biology & drug design

    pub_type: 杂志文章

    doi:10.1111/cbdd.13742

    authors: Bouhedjar K,Boukelia A,Khorief Nacereddine A,Boucheham A,Belaidi A,Djerourou A

    更新日期:2020-09-01 00:00:00

  • Design, Synthesis and Biological Evaluation of Two Opioid Agonist and Cav 2.2 Blocker Multitarget Ligands.

    abstract::N-type voltage-dependent Ca(2+) channels (CaV 2.2) are located at nerve endings in the central and peripheral nervous systems and are strongly associated with the pathological processes of cerebral ischaemia and neuropathic pain. CaV 2.2 blockers such as the ω-conotoxin MVIIA (Prialt) are analgesic and have opioid-spa...

    journal_title:Chemical biology & drug design

    pub_type: 杂志文章

    doi:10.1111/cbdd.12479

    authors: Mollica A,Costante R,Novellino E,Stefanucci A,Pieretti S,Zador F,Samavati R,Borsodi A,Benyhe S,Vetter I,Lewis RJ

    更新日期:2015-08-01 00:00:00

  • Discovery of benzimidazole-based Leishmania mexicana cysteine protease CPB2.8ΔCTE inhibitors as potential therapeutics for leishmaniasis.

    abstract::Chemotherapy is currently the only effective approach to treat all forms of leishmaniasis. However, its effectiveness is severely limited due to high toxicity, long treatment length, drug resistance, or inadequate mode of administration. As a consequence, there is a need to identify new molecular scaffolds and targets...

    journal_title:Chemical biology & drug design

    pub_type: 杂志文章

    doi:10.1111/cbdd.13326

    authors: De Luca L,Ferro S,Buemi MR,Monforte AM,Gitto R,Schirmeister T,Maes L,Rescifina A,Micale N

    更新日期:2018-09-01 00:00:00

  • Development of quinoline-based hybrid as inhibitor of methionine aminopeptidase 1 from Leishmania donovani.

    abstract::Methionine aminopeptidase 1 (MetAP1) is a target for drug discovery against many adversaries and a potential antileishmanial target for its role in N-terminal methionine processing. As an effort towards new inhibitor discovery against methionine aminopeptidase 1 from Leishmania donovani (LdMetAP1), we have synthesized...

    journal_title:Chemical biology & drug design

    pub_type: 杂志文章

    doi:10.1111/cbdd.13783

    authors: Bhat SY,Bhandari S,Thacker PS,Arifuddin M,Qureshi IA

    更新日期:2021-02-01 00:00:00

  • 2-(2,6-Dihalo-phenyl)-3-heteroaryl-2-ylmethyl-1, 3-thiazolidin-4-ones: anti-HIV agents.

    abstract::A diversity of novel 2-aryl-3-heteroaryl-2-ylmethyl-1,3-thiazolidin-4-ones were designed and synthesized by reacting heteroaryl-2-ylmethyl amine with various 2,6-dihalosubstituted benzaldehydes and mercaptoacetic acid. The title compounds were evaluated for human immunodeficiency virus type-1 (HIV-1) reverse transcrip...

    journal_title:Chemical biology & drug design

    pub_type: 杂志文章

    doi:10.1111/j.1747-0285.2008.00683.x

    authors: Rawal RK,Tripathi R,Kulkarni S,Paranjape R,Katti SB,Pannecouque C,De Clercq E

    更新日期:2008-08-01 00:00:00

  • Ensemble-Based Virtual Screening and Experimental Validation of Inhibitors Targeting a Novel Site of Human DNMT1.

    abstract::Human DNA methyltransferase1 (hDNMT1) is responsible for preserving DNA methylation patterns that play important regulatory roles in differentiation and development. Misregulation of DNA methylation has thus been linked to many syndromes, life style diseases, and cancers. Developing specific inhibitors of hDNMT1 is an...

    journal_title:Chemical biology & drug design

    pub_type: 社论

    doi:10.1111/cbdd.12741

    authors: Joshi M,Rajpathak SN,Narwade SC,Deobagkar D

    更新日期:2016-07-01 00:00:00

  • Design of (99m) Tc-DTPA-CLP and preliminary evaluation in rats.

    abstract::Radiopharmaceuticals are localized in (malignant) tumor tissues by different mechanisms. One of these mechanisms, gelatinase enzyme activity, is associated with poor prognosis in cancer patients and potential targets for tumor imaging. There are some gelatinases to be associated with metastatic potential for tumor ima...

    journal_title:Chemical biology & drug design

    pub_type: 杂志文章

    doi:10.1111/cbdd.12253

    authors: Altıparmak B,Lambrecht FY,Er O

    更新日期:2014-03-01 00:00:00

  • Q817G mutation in phosphodiesterase type 5: Conformational analysis and dissociation profile of the inhibitor Tadalafil.

    abstract::Phosphodiesterase type 5 (PDE-5) is an important enzyme involved in the hydrolysis of cyclic guanosine monophosphate (cGMP) to guanosine monophosphate (GMP). The inhibition of this protein leads to the accumulation of cGMP in cells with various biological and therapeutic effects. Several PDE-5 inhibitors exist, with T...

    journal_title:Chemical biology & drug design

    pub_type: 杂志文章

    doi:10.1111/cbdd.13426

    authors: Pires de Oliveira I,Lescano CH,De Nucci G

    更新日期:2019-04-01 00:00:00

  • Fullerene isoniazid conjugate--a tuberculostat with increased lipophilicity: synthesis and evaluation of antimycobacterial activity.

    abstract::A fullerene-isoniazid conjugate has been synthesized by 1, 3 dipolar cycloaddition reaction of fullerene (C(60)) with isonicotinic acid (4-formyl-benzylidene) hydrazide and N-methylglycine. The identity and purity of the compound was confirmed by elemental analysis, (1)H NMR, (13)C NMR and MALDI-TOF mass spectral anal...

    journal_title:Chemical biology & drug design

    pub_type: 信件

    doi:10.1111/j.1747-0285.2009.00804.x

    authors: Kumar A,Patel G,Menon SK

    更新日期:2009-05-01 00:00:00

  • Design and synthesis of a novel peptide for selective detection of cancer cells.

    abstract::Using a minimalist approach, an 11-residue peptide (Peptide 1) tagged with rhodamine fluorophore was designed and synthesized for selective detection of cancer cells. Peptide 1 contains RGD and NGR motifs to bind, respectively, integrins and aminopeptidase CD13, which are over expressed in cancer cells. Surface tensio...

    journal_title:Chemical biology & drug design

    pub_type: 杂志文章

    doi:10.1111/cbdd.13675

    authors: Rajavenkatesh K,Padmaja M,Janani I,Aishwarya S,Purna Sai K,Thennarasu S

    更新日期:2020-06-01 00:00:00

  • Reduction and recombination of fingerprints of different design increase compound recall and the structural diversity of hits.

    abstract::We report an advanced 'hybrid fingerprint' design concept specifically for the purpose of scaffold hopping. The generation of hybrid fingerprints includes two major steps. In the 'fingerprint reduction' step, bit positions of different types of fingerprints (e.g. substructural and pharmacophore fingerprints) are ranke...

    journal_title:Chemical biology & drug design

    pub_type: 杂志文章

    doi:10.1111/j.1747-0285.2009.00930.x

    authors: Nisius B,Bajorath J

    更新日期:2010-02-01 00:00:00