Shikonin derivatives: synthesis and inhibition of human telomerase.

abstract：:Mannose-6-phosphate (M6P)-containing N-linked glycans are essential signaling molecules for sorting hydrolases in eukaryotic cells. Their receptors, especially the cation-independent M6P receptors (CI-MPRs), have emerged as promising protein targets for targeted drug delivery for the treatment of lysosomal storage dis...

journal_title：Bioorganic & medicinal chemistry letters

authors： Liu Y,Marshall J,Li Q,Edwards N,Chen G

更新日期：2013-04-15 00:00:00

abstract：:This study investigated the molecular mechanism of saponarin, a flavone glucoside, in the regulation of insulin sensitivity. Saponarin suppressed the rate of gluconeogenesis and increased cellular glucose uptake in HepG2 and TE671 cells by regulating AMPK. Using an in vitro kinase assay, we showed that saponarin did n...

journal_title：Bioorganic & medicinal chemistry letters

authors： Seo WD,Lee JH,Jia Y,Wu C,Lee SJ

更新日期：2015-11-15 00:00:00

abstract：:A new class of selective nonsteroidal glucocorticoid receptor modulators typified by N-[3-[benzyl-(4-chloro-2-fluoro-benzyl)-amino]-2-methyl-phenyl]-methanesulfonamide 19 has been discovered. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Link JT,Sorensen BK,Patel J,Emery M,Grynfarb M,Goos-Nilsson A

更新日期：2004-05-03 00:00:00

abstract：:(Me)FGC(Bz)DEVD was radiolabeled with technetium-99m in high yield. This tracer was preferentially accumulated in apoptotic cells in the in vitro studies. Tumor uptake occurred in vivo after cisplatin injection due to the apoptosis induction, which not observed in the untreated tumors. Therefore, (99m)Tc-(Me)FGCDEVD i...

journal_title：Bioorganic & medicinal chemistry letters

authors： Bohn P,Mouchard F,Rouvet J,de Boisgrollier AC,Vera P

更新日期：2013-03-01 00:00:00

abstract：:Chronic obstructive pulmonary disease (COPD) is an inflammatory lung disease associated with irreversible progressive airflow limitation. Matrix metalloproteinase-12 (MMP-12) has been characterized to be one of the major proteolytic enzymes to induce airway remodeling, destruction of elastin and the aberrant remodelin...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wu Y,Li J,Wu J,Morgan P,Xu X,Rancati F,Vallese S,Raveglia L,Hotchandani R,Fuller N,Bard J,Cunningham K,Fish S,Krykbaev R,Tam S,Goldman SJ,Williams C,Mansour TS,Saiah E,Sypek J,Li W

更新日期：2012-01-01 00:00:00

abstract：:A series of substituted 2-aminopyridines was prepared and evaluated as inhibitors of human nitric oxide synthases (NOS). 4,6-Disubstitution enhanced both potency and specificity for the inducible NOS with the most potent compound having an IC50 of 28 nM. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hagmann WK,Caldwell CG,Chen P,Durette PL,Esser CK,Lanza TJ,Kopka IE,Guthikonda R,Shah SK,MacCoss M,Chabin RM,Fletcher D,Grant SK,Green BG,Humes JL,Kelly TM,Luell S,Meurer R,Moore V,Pacholok SG,Pavia T,Williams H

更新日期：2000-09-04 00:00:00

abstract：:We screened 1434 small heterocyclic molecules and identified thirteen 2,3,6-trisubstituted quinoxaline derivatives that were able to inhibit the Wnt/β-catenin signal pathway and cell proliferation. In the screen, some of the hit compounds such as the ethylene group-coupled quinoxaline derivatives were shown to hold pr...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lee SB,Park YI,Dong MS,Gong YD

更新日期：2010-10-01 00:00:00

abstract：:Hydroxy urea moieties are introduced as a new class of bradykinin B(1) receptor antagonists. First, the SAR of the lead compound was systematically explored. Subsequent optimization resulted in the identification of several biaryl-based hydroxyurea bradykinin B(1) receptor antagonists with low-nanomolar activity and v...

journal_title：Bioorganic & medicinal chemistry letters

authors： Schnatbaum K,Schaudt M,Stragies R,Pfeifer JR,Gibson C,Locardi E,Scharn D,Richter U,Kalkhof H,Dinkel K,Zischinsky G

更新日期：2010-02-01 00:00:00

abstract：:A novel caspase-3 substrate N-Ac-DEVD-N'-MC-R110, which is a fluorogenic substrate cleavable in a single step, has been prepared. It has a significantly higher enzyme turnover rate and sensitivity for detecting caspase-3 activity both in solution and living cells than existing fluorogenic substrates. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wang ZQ,Liao J,Diwu Z

更新日期：2005-05-02 00:00:00

abstract：:A series of 43, 3a,4-dihydro-3H-indeno[1,2-c]pyrazole-2-carboxamide/carbothioamide analogues (D01-D43) were analysed using Petra, Osiris, Molinspiration and ALOGPS (POMA) to identify pharmacophore, toxicity prediction, lipophilicity and bioactivity. All the compounds were evaluated for anti-HIV activity. 3-(4-Chloroph...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ahsan MJ,Govindasamy J,Khalilullah H,Mohan G,Stables JP

更新日期：2012-12-01 00:00:00

abstract：:A series of a novel hybrid compounds between nitazoxanide and N-methylbenzimidazole were synthesized starting from the corresponding N-methyl-2-nitroanilines. The new hybrid compounds (1-13) were evaluated in vitro against Giardia intestinalis, Entamoeba histolytica, Trichomonas vaginalis. NTZ, MTZ and ABZ were used a...

journal_title：Bioorganic & medicinal chemistry letters

authors： Soria-Arteche O,Hernández-Campos A,Yépez-Mulia L,Trejo-Soto PJ,Hernández-Luis F,Gres-Molina J,Maldonado LA,Castillo R

更新日期：2013-12-15 00:00:00

abstract：:The eryA gene of the bacterial pathogen Brucella abortus has been functionally expressed in Escherichia coli. The resultant EryA was shown to catalyze the ATP-dependent conversion of erythritol to L-erythritol-4-phosphate (L-E4P). The steady state kinetic parameters of this reaction were determined and the enzyme was ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lillo AM,Tetzlaff CN,Sangari FJ,Cane DE

更新日期：2003-02-24 00:00:00

abstract：:Many types of cancer, including glioma, melanoma, NSCLC, among others, are resistant to apoptosis induction and poorly responsive to current therapies with propaptotic agents. We describe a series of 2,3-disubstituted indoles, which display cytostatic rather than cytotoxic effects in cancer cells, and serve as a new c...

journal_title：Bioorganic & medicinal chemistry letters

authors： Magedov IV,Lefranc F,Frolova LV,Banuls LM,Peretti AS,Rogelj S,Mathieu V,Kiss R,Kornienko A

更新日期：2013-06-01 00:00:00

abstract：:The protein kinase TNK2 (ACK1) is an emerging drug target for a variety of indications, in particular for cancer where it plays a key role transmitting cell survival, growth and proliferative signals via modification of multiple downstream effectors by unique tyrosine phosphorylation events. Scaffold morphing based on...

journal_title：Bioorganic & medicinal chemistry letters

authors： Li Z,Powell CE,Groendyke BJ,Gero TW,Feru F,Feutrill J,Chen B,Li B,Szabo H,Gray NS,Scott DA

更新日期：2020-10-01 00:00:00

abstract：:In this work we present the synthesis, aqueous solubility and stability, hydrolysis by alkaline phosphatase, and in vivo fasciolicidal activity in sheep of a highly water soluble phosphate salt prodrug of triclabendazole (MFR-5). The aqueous solubility of MFR-5 at pH 7 was 88,000-fold that of triclabendazole. MFR-5 sh...

journal_title：Bioorganic & medicinal chemistry letters

authors： Flores-Ramos M,Ibarra-Velarde F,Jung-Cook H,Hernández-Campos A,Vera-Montenegro Y,Castillo R

更新日期：2017-02-01 00:00:00

abstract：:The pRBM4 cosmid, which harbors a putative cluster of genes spanning a 31.8-kb chromosomal region of the ribostamycin producer Streptomyces ribosidificus ATCC 21294, was heterologously expressed in Streptomyces lividans TK24. ESI-MS/MS, HPLC, and LC-ESI MS analyses showed that the transformation gave rise to ribostamy...

journal_title：Bioorganic & medicinal chemistry letters

authors： Subba B,Kurumbang NP,Jung YS,Yoon YJ,Lee HC,Liou K,Sohng JK

更新日期：2007-04-01 00:00:00

abstract：:The same two major CYP mediated metabolites of DG-051 were produced in the presence of rat, dog, monkey and human liver microsomes. Their respective structures were hypothesized based on mass spectrometry data correlated with the parent structure and confirmed by comparison with authentic synthetic samples. The number...

journal_title：Bioorganic & medicinal chemistry letters

authors： Enache LA,Zhang J,Sullins DW,Kennedy I,Onua E,Zembower DE,Muellner FW,Singh J,Kiselyov AS

更新日期：2009-11-15 00:00:00

abstract：:Sphingosine-1-phosphate (S1P) is a ubiquitous, endogenous small molecule that is synthesized by two isoforms of sphingosine kinase (SphK1 and 2). Intervention of the S1P signaling pathway has attracted significant attention because alteration of S1P levels is linked to several disease states including cancer, fibrosis...

journal_title：Bioorganic & medicinal chemistry letters

authors： Congdon MD,Childress ES,Patwardhan NN,Gumkowski J,Morris EA,Kharel Y,Lynch KR,Santos WL

更新日期：2015-11-01 00:00:00

abstract：:The discovery, synthesis, and SAR of chromanes as ER alpha subtype selective ligands are described. X-ray studies revealed that the origin of the ER alpha-selectivity resulted from a C-4 trans methyl substitution to the cis-2,3-diphenyl-chromane platform. Selected compounds from this class demonstrated very potent in ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Tan Q,Blizzard TA,Morgan JD 2nd,Birzin ET,Chan W,Yang YT,Pai LY,Hayes EC,DaSilva CA,Warrier S,Yudkovitz J,Wilkinson HA,Sharma N,Fitzgerald PM,Li S,Colwell L,Fisher JE,Adamski S,Reszka AA,Kimmel D,DiNinno F,Rohre

更新日期：2005-03-15 00:00:00

abstract：:Twenty-five novel pregnenolone/2-cyanoacryloyl conjugates (6-30) were designed and prepared, with the aim of developing novel anticancer drugs with dual NF-κB inhibitory and anti-proliferative activities. Compounds 22 and 27-30 showed inhibition against TNF-α-induced NF-κB activation in luciferase assay, which was con...

journal_title：Bioorganic & medicinal chemistry letters

authors： Song JL,Zhang J,Liu CL,Liu C,Zhu KK,Yang FF,Liu XG,Figueiró Longo JP,Alexandre Muehlmann L,Azevedo RB,Zhang YY,Guo YW,Jiang CS,Zhang H

更新日期：2017-10-15 00:00:00

abstract：:Betulinic acid has been modified at C-3, C-20, and C-28 positions and the toxicity of the derivatives has been evaluated against cultured human melanoma (MEL-2) and human epidermoid carcinoma of the mouth (KB) cell lines. This preliminary investigation demonstrates that simple modifications of the parent structure of ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kim DS,Pezzuto JM,Pisha E

更新日期：1998-07-07 00:00:00

abstract：:A protein without natural binding functions was engineered to bind HIV-1 integrase. Phage display selections applied a library of variants based on the C-terminal domain of the eye lens protein human γS-crystallin. Multiple loop regions were altered to encode libraries with ≈3.6 × 10(11) different variants. A crystall...

journal_title：Bioorganic & medicinal chemistry letters

authors： Moody IS,Verde SC,Overstreet CM,Edward Robinson W Jr,Weiss GA

更新日期：2012-09-01 00:00:00

abstract：:8-Iodo-11-(4-methylpiperazino)-5H-dibenzo[b,e][1,4]-diazepine: Iozapine, a potential D(4)-receptor ligand was synthesized using oxidative iodo-destannylation reaction. The preliminary biodistribution studies of radioiodinated iozapine have shown that the compound is taken up in the brains of mice and rabbits. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Joshua AV,Sharma SK,Strelkov A,Scott JR,Martin-Iverson MT,Abrams DN,Silverstone PH,McEwan AJ

更新日期：2007-07-15 00:00:00

abstract：:Novel quinolone-macrocycle conjugates displayed submicromolar antibacterial activity against Escherichia coli and Staphylococcus aureus bacterial strains. An analogous open-chain structure was not active at 100 microM against the same pathogenic strains. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Jefferson EA,Swayze EE,Osgood SA,Miyaji A,Risen LM,Blyn LB

更新日期：2003-05-19 00:00:00

abstract：:Aryl hydroxylamine derivatives have been synthesised that are some of the most potent inhibitors of hCMV protease prepared to date (IC50 14-60 nM). Mass spectrometry studies indicate that oxazinone derived hydroxylamines inhibit the enzyme by acylation of Ser132 whereas non-oxazinone derived hydroxylamines appear to i...

journal_title：Bioorganic & medicinal chemistry letters

authors： Smith DG,Gribble AD,Haigh D,Ife RJ,Lavery P,Skett P,Slingsby BP,Stacey R,Ward RW,West A

更新日期：1999-11-01 00:00:00

abstract：:A series of 8-heteroarylthiomethyldipyridodiazepinone derivatives were prepared and evaluated for their antiviral profile against wild type virus and the important K103N/Y181C mutant as an indicator for broad activity. 2,6-Dimethylpyridine derivative 16 was found to have a good pharmacokinetic profile in spite of poor...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yoakim C,Bonneau PR,Déziel R,Doyon L,Duan J,Guse I,Landry S,Malenfant E,Naud J,Ogilvie WW,O'Meara JA,Plante R,Simoneau B,Thavonekham B,Bös M,Cordingley MG

更新日期：2004-02-09 00:00:00

abstract：:Thirty-two new derivatives of cerpegin (1,1,5-trimethylfuro[3,4-c]pyridine-3,4-dione) were designed and synthesized in high yield by a new method, combining several C(1) and N(5) substituents. All compounds were tested for their inhibitory effect on the CT-L, T-L and PA proteolytic activities of a purified mammalian 2...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hovhannisyan A,Pham TH,Bouvier D,Qin L,Melikyan G,Reboud-Ravaux M,Bouvier-Durand M

更新日期：2013-05-01 00:00:00

abstract：:Several imidazole-based cyclohexyl amides were identified as potent CB-1 antagonists, but they exhibited poor oral exposure in rodents. Incorporation of a hydroxyl moiety on the cyclohexyl ring provided a dramatic improvement in oral exposure, together with a ca. 10-fold decrease in potency. Further optimization provi...

journal_title：Bioorganic & medicinal chemistry letters

authors： Smith RA,Fathi Z,Achebe F,Akuche C,Brown SE,Choi S,Fan J,Jenkins S,Kluender HC,Konkar A,Lavoie R,Mays R,Natoli J,O'Connor SJ,Ortiz AA,Su N,Taing C,Tomlinson S,Tritto T,Wang G,Wirtz SN,Wong W,Yang XF,Ying S,

更新日期：2007-05-15 00:00:00

abstract：:Eight new isocoumarin glycosides (1-8) were obtained from the solid culture of the wetland soil-derived fungus Metarhizium anisopliae (No. DTH12-10). Their chemical structures were elucidated by analyses of HR ESI-TOF MS, (1)H, (13)C NMR, (1)H-(1)H COSY, HSQC, and HMBC spectra. The absolute configurations were determi...

journal_title：Bioorganic & medicinal chemistry letters

authors： Tian JF,Li PJ,Li XX,Sun PH,Gao H,Liu XZ,Huang P,Tang JS,Yao XS

更新日期：2016-03-01 00:00:00

abstract：:Numerous potent P2X3 antagonists have been discovered and the therapeutic potential of P2X3 antagonism already comprises proof-of-concept data obtained in clinical trials with the most advanced compound. We have lately reported the discovery and optimization of thia-triaza-tricycle compounds with potent P2X3 antagonis...

journal_title：Bioorganic & medicinal chemistry letters

authors： Szántó G,Makó A,Vágó I,Hergert T,Bata I,Farkas B,Kolok S,Vastag M

更新日期：2016-08-15 00:00:00