abstract：:Lamin A contributes to the structure of nuclei in all mammalian cells and plays an important role in cell division and migration. Mature lamin A is derived from a farnesylated precursor protein, known as prelamin A, which undergoes post-translational cleavage catalyzed by the zinc metalloprotease STE24 (ZPMSTE24). Acc...

journal_title：Bioorganic & medicinal chemistry

authors： Matralis AN,Xanthopoulos D,Huot G,Lopes-Paciencia S,Cole C,de Vries H,Ferbeyre G,Tsantrizos YS

更新日期：2018-11-01 00:00:00

abstract：:Carbohydrates are the most prominent features of the cell's exterior-they are the cell's "face" and serve as the cell's identification card. The features of cell surface glycans (e.g. glycoproteins, glycolipids, polysaccharides) can be read by proteins, other cells, or organisms. In all of these contexts, glycan-bindi...

journal_title：Bioorganic & medicinal chemistry

authors： Kiessling LL

更新日期：2018-10-15 00:00:00

abstract：:Janus kinases (JAKs) are considered promising targets for the treatment of autoimmune diseases including rheumatoid arthritis (RA) due to their important role in multiple cytokine receptor signaling pathways. Recently, several JAK inhibitors have been developed for the treatment of RA. Here, we describe the identifica...

journal_title：Bioorganic & medicinal chemistry

authors： Hamaguchi H,Amano Y,Moritomo A,Shirakami S,Nakajima Y,Nakai K,Nomura N,Ito M,Higashi Y,Inoue T

更新日期：2018-10-01 00:00:00

abstract：:Sustained activation of the Janus kinase-signal transducers and activators of transcription (JAK-STAT) pathway contributed to the progression of cancer and liver diseases. STAT3 signaling inhibitor has been extensively investigated for pharmacological use. We synthesized a series of andrographolide derivatives, and ch...

journal_title：Bioorganic & medicinal chemistry

authors： Chen SR,Li F,Ding MY,Wang D,Zhao Q,Wang Y,Zhou GC,Wang Y

更新日期：2018-10-01 00:00:00

abstract：:Amyloid-β (Aβ) and tau protein are two crucial hallmarks in Alzheimer's disease (AD). Their aggregation forms are thought to be toxic to the neurons in the brain. A series of new 1,2,3,4-tetrahydro-1-acridone analogues were designed, synthesized, and evaluated as potential dual inhibitors for Aβ and tau aggregation. I...

journal_title：Bioorganic & medicinal chemistry

authors： Lv P,Xia CL,Wang N,Liu ZQ,Huang ZS,Huang SL

更新日期：2018-09-01 00:00:00

abstract：:Tyrosyl-DNA phosphodiesterase 1 (Tdp1) is a repair enzyme for stalled DNA-topoisomerase 1 (Top 1) cleavage complexes and other 3'-end DNA lesions. Tdp1 is a promising target for anticancer therapy, since it can repair DNA lesions caused by Top1 inhibitors leading to drug resistance. Hence, Tdp1 inhibition should resul...

journal_title：Bioorganic & medicinal chemistry

authors： Zakharova O,Luzina O,Zakharenko A,Sokolov D,Filimonov A,Dyrkheeva N,Chepanova A,Ilina E,Ilyina A,Klabenkova K,Chelobanov B,Stetsenko D,Zafar A,Eurtivong C,Reynisson J,Volcho K,Salakhutdinov N,Lavrik O

更新日期：2018-08-15 00:00:00

abstract：:Pregnane X receptor (PXR) is a ligand-dependent transcription factor that is considered to be a potential therapeutic target for multiple diseases. Herein, we report the development and structure-activity relationship studies of a new series of hPXR agonists. Focusing on our recently developed silanol-sulfonamide scaf...

journal_title：Bioorganic & medicinal chemistry

authors： Toyama H,Shirakawa H,Komai M,Hashimoto Y,Fujii S

更新日期：2018-08-15 00:00:00

abstract：:A series of 2-(3,5-substituted 4-aminophenyl)acetamide and propanamide derivatives were investigated as human TRPV1 antagonists. The analysis of the structure-activity relationship indicated that 2-(3,5-dihalo 4-aminophenyl)acetamide analogues displayed excellent antagonism of hTRPV1 activation by capsaicin and showed...

journal_title：Bioorganic & medicinal chemistry

authors： Kim C,Ann J,Lee S,Kim E,Choi S,Blumberg PM,Frank-Foltyn R,Bahrenberg G,Stockhausen H,Christoph T,Lee J

更新日期：2018-08-15 00:00:00

abstract：:Two series of ω-phenoxy contained acylhydroxamic acids as novel urease inhibitors were designed and synthesized. Biological activity evaluations revealed that ω-phenoxypropinoylhydroxamic acids were more active than phenoxyacetohydroxamic acids. Out of these compounds, 3-(3,4-dichlorophenoxy)propionylhydroxamic acid c...

journal_title：Bioorganic & medicinal chemistry

authors： Ni WW,Liu Q,Ren SZ,Li WY,Yi LL,Jing H,Sheng LX,Wan Q,Zhong PF,Fang HL,Ouyang H,Xiao ZP,Zhu HL

更新日期：2018-08-07 00:00:00

abstract：:We described the discovery and optimization of a novel series of pyrimidopyrimidine derivatives as G-protein coupled receptor 119 (GPR119) agonists against type 2 diabetes. Most designed compounds displayed significant GPR119 agonistic activities. Optimized analogues 15a and 21e exhibited highly potent agonistic activ...

journal_title：Bioorganic & medicinal chemistry

authors： Fang Y,Xu J,Li Z,Yang Z,Xiong L,Jin Y,Wang Q,Xie S,Zhu W,Chang S

更新日期：2018-08-07 00:00:00

abstract：:Sphingolipids are ubiquitous and abundant components of all eukaryotic and some prokaryotic organisms. Sphingolipids show a large structural variety not only between the different species, but also within an individual cell. This variety is not limited to alterations in the polar headgroups of e.g. glycosphingolipids,...

journal_title：Bioorganic & medicinal chemistry

authors： Saied EM,Le TL,Hornemann T,Arenz C

更新日期：2018-08-07 00:00:00

abstract：:Activation of the nuclear farnesoid X receptor (FXR) which acts as cellular bile acid sensor has been validated as therapeutic strategy to counter liver disorders such as non-alcoholic steatohepatitis by the clinical efficacy of obeticholic acid. FXR antagonism, in contrast, is less well studied and potent small molec...

journal_title：Bioorganic & medicinal chemistry

authors： Schmidt J,Schierle S,Gellrich L,Kaiser A,Merk D

更新日期：2018-08-07 00:00:00

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

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

abstract：:Higher-order structures of nucleic acids have become widely noted for their biological consequences and the discovery of an alkylating small molecule for these structures has been of interest due to its therapeutic potential. We previously developed the vinyldiaminotriazine (VDAT)-acridine conjugate as a T-T mismatch ...

journal_title：Bioorganic & medicinal chemistry

authors： Hazemi ME,Onizuka K,Kobayashi T,Usami A,Sato N,Nagatsugi F

更新日期：2018-07-23 00:00:00

abstract：:The over-expression of aminopeptidase N on diverse malignant cells is associated with the tumor angiogenesis and metastasis. In this report, one new series of leucine ureido derivatives containing the triazole moiety was designed, synthesized and evaluated as APN inhibitors. Among them, compound 13v showed the best AP...

journal_title：Bioorganic & medicinal chemistry

authors： Cao J,Ma C,Zang J,Gao S,Gao Q,Kong X,Yan Y,Liang X,Ding Q,Zhao C,Wang B,Xu W,Zhang Y

更新日期：2018-07-23 00:00:00

abstract：:In the amyloid cascade hypothesis, β-amyloid (Aβ) plaques is one of the major pathological biomarkers in the Alzheimer's disease (AD) brain. We report the synthesis and evaluation of novel radiofluorinated chalcones, [18F]4-dimethylamino-4'-fluoro-chalcone ([18F]DMFC) and [18F]4'-fluoro-4-methylamino-chalcone ([18F]FM...

journal_title：Bioorganic & medicinal chemistry

authors： Kaide S,Ono M,Watanabe H,Shimizu Y,Nakamoto Y,Togashi K,Yamaguchi A,Hanaoka H,Saji H

更新日期：2018-07-23 00:00:00

abstract：:In the present study, a new class of compounds containing pyrido[3,4-d]pyrimidine scaffold with an acrylamide moiety was designed as irreversible EGFR-TKIs to overcome acquired EGFR-T790M resistance. The most promising compound 25h inhibited HCC827 and H1975 cells growth with the IC50 values of 0.025 μM and 0.49 μM, r...

journal_title：Bioorganic & medicinal chemistry

authors： Zhang H,Wang J,Zhao HY,Yang XY,Lei H,Xin M,Cao YX,Zhang SQ

更新日期：2018-07-23 00:00:00

abstract：:A series of novel anthranilic diamides derivatives (7a-s) containing halogen, trifluoromethyl group and cyano group were designed, synthesized, and characterized by melting point, 1H NMR, 13C NMR and elemental analyses. The bioactivity revealed that most of them showed moderate to excellent activities against oriental...

journal_title：Bioorganic & medicinal chemistry

authors： Liu JB,Li FY,Dong JY,Li YX,Zhang XL,Wang YH,Xiong LX,Li ZM

更新日期：2018-07-23 00:00:00

abstract：:In this study a new set of thiazolo[5,4-d]pyrimidine derivatives was synthesized. These derivatives bear different substituents at positions 2 and 5 of the thiazolopyrimidine core while maintaining a free amino group at position-7. The new compounds were tested for their affinity and potency at human (h) A1, A2A, A2B ...

journal_title：Bioorganic & medicinal chemistry

authors： Varano F,Catarzi D,Falsini M,Vincenzi F,Pasquini S,Varani K,Colotta V

更新日期：2018-07-23 00:00:00

abstract：:We report an inhibitor of the homodimeric protein-protein interaction of the BCL6 oncoprotein, identified from a genetically encoded SICLOPPS library of 3.2 million cyclic hexapeptides in combination with a bacterial reverse two-hybrid system. This cyclic peptide is shown to bind the BTB domain of BCL6, disrupts its h...

journal_title：Bioorganic & medicinal chemistry

authors： Osher EL,Castillo F,Elumalai N,Waring MJ,Pairaudeau G,Tavassoli A

更新日期：2018-07-15 00:00:00

abstract：:It looks that a new era of antimicrobial peptides (AMPs) started with the discovery of teixobactin, which is a "head to side-chain" cyclodepsipeptide. It was isolated from a soil gram-negative b-proteobacteria by means of a revolutionary technique. Since there, several groups have developed synthetic strategies for ef...

journal_title：Bioorganic & medicinal chemistry

authors： Abdel Monaim SAH,Jad YE,El-Faham A,de la Torre BG,Albericio F

更新日期：2018-06-01 00:00:00

abstract：:Pharmacokinetic (PK) extension is no longer just a means to create improved second generation biologics (so-called biobetters), but constitutes an accepted strategy in biopharmaceutical drug development today. Although PEGylation has become a widely applied methodology to furnish therapeutic proteins and peptides with...

journal_title：Bioorganic & medicinal chemistry

authors： Gebauer M,Skerra A

更新日期：2018-06-01 00:00:00

abstract：:Infectious diseases and cancers are leading causes of death and pose major challenges to public health. The human peptidome encompasses millions of compounds that display an enormous structural and functional diversity and represents an excellent source for the discovery of endogenous agents with antimicrobial and/or ...

journal_title：Bioorganic & medicinal chemistry

authors： Bosso M,Ständker L,Kirchhoff F,Münch J

更新日期：2018-06-01 00:00:00

abstract：:We report a series of tubulin targeting agents, some of which demonstrate potent antiproliferative activities. These analogs were designed to optimize the antiproliferative activity of 1 by varying the heteroatom substituent at the 4'-position, the basicity of the 4-position amino moiety, and conformational restrictio...

journal_title：Bioorganic & medicinal chemistry

authors： Xiang W,Choudhary S,Hamel E,Mooberry SL,Gangjee A

更新日期：2018-05-15 00:00:00

abstract：:Novel pyrazole carboxamides with a diarylamine-modified scaffold were modified based on the bixafen (Bayer) fungicide, which has excellent activity against Rhizoctonia solani, Rhizoctonia cerealis and Sclerotinia sclerotiorum. To discover the potential insecticidal activity of these novel pyrazole carboxamides, the pr...

journal_title：Bioorganic & medicinal chemistry

authors： Ren Y,Yang N,Yue Y,Jin H,Tao K,Hou T

更新日期：2018-05-15 00:00:00

abstract：:REV1 protein is a mutagenic DNA damage tolerance (DDT) mediator and encodes two ubiquitin-binding motifs (i.e., UBM1 and UBM2) that are essential for the DDT function. REV1 interacts with K164-monoubiquitinated PCNA (UbPCNA) in cells upon DNA-damaging stress. By using AlphaScreen assays to detect inhibition of REV1 an...

journal_title：Bioorganic & medicinal chemistry

authors： Vanarotti M,Evison BJ,Actis ML,Inoue A,McDonald ET,Shao Y,Heath RJ,Fujii N

更新日期：2018-05-15 00:00:00

abstract：:The binding stoichiometry, binding constants, and inclusion mode of some water-soluble negatively charged cyclodextrin derivatives, i.e. heptakis-[6-deoxy-6-(3-sulfanylpropanoic acid)]-β-cyclodextrin(H1), heptakis-[6-deoxy-6-(2-sulfanylacetic acid)]-β-cyclodextrin(H2), mono-[6-deoxy-6-(3-sulfanylpropanoic acid)]-β-cyc...

journal_title：Bioorganic & medicinal chemistry

authors： Cheng JG,Yu HJ,Chen Y,Liu Y

更新日期：2018-05-15 00:00:00

abstract：:A series of arylnaphthalene lignan lactones based on the structure of the phyllanthusmins, a class of potent natural products possessing diphyllin as the aglycone, has been synthesized and screened for activity against multiple cancer cell lines. SAR exploration was performed on both the carbohydrate and lactone moiet...

journal_title：Bioorganic & medicinal chemistry

authors： Woodard JL,Huntsman AC,Patel PA,Chai HB,Kanagasabai R,Karmahapatra S,Young AN,Ren Y,Cole MS,Herrera D,Yalowich JC,Kinghorn AD,Burdette JE,Fuchs JR

更新日期：2018-05-15 00:00:00

abstract：:Borrelidin A (1) is produced by several species of Streptomyces and within its bioactive scaffold, the vinylic nitrile moiety is essential for activity. We report herein newly discovered members of the borrelidin family, borrelidin F (2), borrelidin G (3), borrelidin H (4) and borrelidin I (5); all were isolated from ...

journal_title：Bioorganic & medicinal chemistry

authors： Sun J,Shao J,Sun C,Song Y,Li Q,Lu L,Hu Y,Gui C,Zhang H,Ju J

更新日期：2018-05-01 00:00:00

abstract：:Replacing the naphthalene C-unit of the anti-tuberculosis drug bedaquiline with a range of bicyclic heterocycles of widely differing lipophilicity gave analogs with a 4.5-fold range in clogP values. The biological results for these compounds indicate on average a lower clogP limit of about 5.0 in this series for reten...

journal_title：Bioorganic & medicinal chemistry

authors： Sutherland HS,Tong AST,Choi PJ,Conole D,Blaser A,Franzblau SG,Cooper CB,Upton AM,Lotlikar MU,Denny WA,Palmer BD

更新日期：2018-05-01 00:00:00

abstract：:Pin1 (Protein interacting with NIMA1) is a cis-trans isomerase and promotes the amide bond rotation of phosphoSer/Thr-Pro motifs in its substrates. Inhibition of Pin1 might be a novel strategy for developing anticancer agents. Herein, a series of pyrimidine derivatives were synthesized and their Pin1 inhibitory activi...

journal_title：Bioorganic & medicinal chemistry

authors： Cui G,Jin J,Chen H,Cao R,Chen X,Xu B

更新日期：2018-05-01 00:00:00

abstract：:The fungus Aspergillus japonicus MF275 produces himeic acid A (1), containing a 4-pyrone ring, along with its congeners, himeic acids B (2) and C (3). During culture, 1 was gradually converted to 3, the corresponding 4-pyridone derivative. A study of the relationship between the culture pH and the fungal metabolites s...

journal_title：Bioorganic & medicinal chemistry

authors： Katsuki A,Kato H,Tahara Y,Hashimoto M,Fujii I,Tsukamoto S

更新日期：2018-05-01 00:00:00

abstract：:In recent years, inhibition of HDAC6 became a promising therapeutic strategy for the treatment of cancer and HDAC6 inhibitors were considered to be potent anti-cancer agents. In this work, celecoxib showed moderate degree of HDAC6 inhibition activity and selectivity in preliminary enzyme inhibition activity assay. A s...

journal_title：Bioorganic & medicinal chemistry

authors： Yang J,Cheng G,Xu Q,Luan S,Wang S,Liu D,Zhao L

更新日期：2018-05-01 00:00:00

abstract：:Natural compounds are often structurally complex and their synthesis is still highly challenging. The review intends to give an overview on developments in biotechnology and their role for the production of natural products and active agents. In vitro and in vivo methods are presented side by side beginning with rathe...

journal_title：Bioorganic & medicinal chemistry

authors： Classen T,Pietruszka J

更新日期：2018-04-01 00:00:00

abstract：:A facile, one-pot enzymatic glycan remodeling of antibody rituximab to produce homogeneous high-mannose and hybrid type antibody glycoforms is described. This method was based on the unique substrate specificity of the endoglycosidase S (Endo-S) from Streptococcus pyogenes. While Endo-S efficiently hydrolyzes the bi-a...

journal_title：Bioorganic & medicinal chemistry

authors： Tong X,Li T,Orwenyo J,Toonstra C,Wang LX

更新日期：2018-04-01 00:00:00

abstract：:Many therapeutically-relevant protein-protein interactions (PPIs) have been reported that feature a helix and helix-binding cleft at the interface. Given this, different approaches to disrupting such PPIs have been developed. While short peptides (<15 amino acids) typically do not fold into a stable helix, researchers...

journal_title：Bioorganic & medicinal chemistry

authors： Tennyson RL,Walker SN,Ikeda T,Harris RS,McNaughton BR

更新日期：2018-03-15 00:00:00

abstract：:Changes in pH resulting in modifications of charge can dramatically alter the folding and interaction of proteins. This article probes the effects of charge and hydrophobicity on the oligomerization of macrocyclic β-sheet peptides derived from residues 11-17 of IAPP (RLANFLV). Previous studies have shown that a macroc...

journal_title：Bioorganic & medicinal chemistry

authors： Wang Y,Truex NL,Vo NDP,Nowick JS

更新日期：2018-03-15 00:00:00

abstract：:We synthesized the biotinylated chondroitin sulfate tetrasaccharides CS-CC [-3)βGalNAc6S(1-4)βGlcA(1-]2 and CS-DD [-3)βGalNAc6S(1-4)βGlcA2S(1-]2 which possess sulfate groups at O-6 of GalNAc and an additional sulfate group at O-2 of GlcA, respectively. We also analyzed interactions among CS-CC and CS-DD and the antibo...

journal_title：Bioorganic & medicinal chemistry

authors： Matsushita K,Nakata T,Takeda-Okuda N,Nadanaka S,Kitagawa H,Tamura JI

更新日期：2018-03-01 00:00:00

abstract：:Synthetic modification of cyclosporin A at P3-P4 positions led to the discovery of NIM258, a next generation cyclophilin inhibitor with excellent anti-hepatitis C virus potency, with decreased transporter inhibition, and pharmacokinetics suitable for coadministration with other drugs. Herein is disclosed the evolution...

journal_title：Bioorganic & medicinal chemistry

authors： Fu J,Becker C,Cao L,Capparelli M,Denay R,Fujimoto R,Gai Y,Gao Z,Guenat C,Karur S,Kim H,Li W,Li X,Li W,Lochmann T,Lu A,Lu P,Luneau A,Meier N,Mergo W,Ng S,Parker D,Peng Y,Riss B,Rivkin A,Roggo S,Schroede

更新日期：2018-02-15 00:00:00

abstract：:Novel reversed isoniazid (RINH) agents were synthesized by covalently linking isoniazid with various efflux pump inhibitor (EPI) cores and their structural motifs. These RINH agents were then evaluated for anti-mycobacterial activity against sensitive, isoniazid mono-resistant and MDR clinical isolates of M. tuberculo...

journal_title：Bioorganic & medicinal chemistry

authors： Kumar M,Singh K,Ngwane AH,Hamzabegovic F,Abate G,Baker B,Wiid I,Hoft DF,Ruminski P,Chibale K

更新日期：2018-02-15 00:00:00