abstract：:We report the kinetic properties and sulfonamide inhibition profile of an α-carbonic anhydrase (CA, EC 4.2.1.1), named CruCA4, identified in the red coral Corallium rubrum. This isoform is involved in the biomineralization process leading to the formation of a calcium carbonate skeleton. Experiments performed on the r...

journal_title：Bioorganic & medicinal chemistry

authors： Del Prete S,Vullo D,Zoccola D,Tambutté S,Capasso C,Supuran CT

更新日期：2017-07-01 00:00:00

abstract：:Histone acetylation is an extensively investigated post-translational modification that plays an important role as an epigenetic regulator. It is controlled by histone acetyl transferases (HATs) and histone deacetylases (HDACs). The overexpression of HDACs and consequent hypoacetylation of histones have been observed ...

journal_title：Bioorganic & medicinal chemistry

authors： Kim B,Ratnayake R,Lee H,Shi G,Zeller SL,Li C,Luesch H,Hong J

更新日期：2017-06-15 00:00:00

abstract：:Two series of quinazoline derivatives bearing aryl semicarbazone scaffolds (9a-o and 10a-o) were designed, synthesized and evaluated for the IC50 values against four cancer cell lines (A549, HepG2, MCF-7 and PC-3). The selected compound 9o was further evaluated for the inhibitory activity against EGFR kinases. Four of...

journal_title：Bioorganic & medicinal chemistry

authors： Tu Y,Wang C,Xu S,Lan Z,Li W,Han J,Zhou Y,Zheng P,Zhu W

更新日期：2017-06-15 00:00:00

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

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

abstract：:We recently reported that 4-epi-jaspine B exhibits potent inhibitory activity towards sphingosine kinases (SphKs). In this study, we investigated the effects of modifying the 2-alkyl group, as well as the functional groups on the THF ring of 4-epi-jaspine B using a diversity-oriented synthesis approach based on a late...

journal_title：Bioorganic & medicinal chemistry

authors： Ohno H,Honda M,Hamada N,Miyagaki J,Iwata A,Otsuki K,Maruyama T,Nakamura S,Nakanishi I,Inuki S,Fujii N,Oishi S

更新日期：2017-06-15 00:00:00

abstract：:A growing number of studies have demonstrated that interleukin (IL)-6 plays pathological roles in the development of chronic inflammatory disease and autoimmune disease by activating innate immune cells and by stimulating adaptive inflammatory T cells. So, suppression of IL-6 function may be beneficial for prevention ...

journal_title：Bioorganic & medicinal chemistry

authors： Kim D,Won HY,Hwang ES,Kim YK,Choo HP

更新日期：2017-06-15 00:00:00

abstract：:The proteasome, a validated cellular target for cancer, is central for maintaining cellular homeostasis, while fatty acid synthase (FAS), a novel target for numerous cancers, is responsible for palmitic acid biosynthesis. Perturbation of either enzymatic machine results in decreased proliferation and ultimately cellul...

journal_title：Bioorganic & medicinal chemistry

authors： Zhu M,Harshbarger WD,Robles O,Krysiak J,Hull KG,Cho SW,Richardson RD,Yang Y,Garcia A,Spiegelman L,Ramirez B,Wilson CT,Yau JA,Moore JT,Walker CB,Sacchettini JC,Liu WR,Sieber SA,Smith JW,Romo D

更新日期：2017-06-01 00:00:00

abstract：:A series of novel tetrahydropyrazolopyridone derivatives containing 1,3,4-triazole, triazolylmethyl, and partially saturated heterocyclic moieties as P2 binding element was designed, synthesized, and evaluated in vitro for anticoagulant activity in human and rabbit plasma. All compounds showed moderate to significant ...

journal_title：Bioorganic & medicinal chemistry

authors： Sun X,Hong Z,Liu M,Guo S,Yang D,Wang Y,Lan T,Gao L,Qi H,Gong P,Liu Y

更新日期：2017-05-15 00:00:00

abstract：:A novel series of arylsulfonamide derivatives of (aryloxy)propyl piperidines was designed to obtain potent 5-HT7R antagonists. Among the compounds evaluated herein, 3-chloro-N-{1-[3-(1,1-biphenyl-2-yloxy)2-hydroxypropyl]piperidin-4-yl}benzenesulfonamide (25) exhibited antagonistic properties at 5-HT7R and showed selec...

journal_title：Bioorganic & medicinal chemistry

authors： Canale V,Partyka A,Kurczab R,Krawczyk M,Kos T,Satała G,Kubica B,Jastrzębska-Więsek M,Wesołowska A,Bojarski AJ,Popik P,Zajdel P

更新日期：2017-05-15 00:00:00

abstract：:This study measured the antiplasmodial activity of nine zinc-dipicolylamine (ZnDPA) complexes against three strains of Plasmodium falciparum, the causative parasite of malaria. Growth inhibition assays showed significant activity against all tested strains, with 50% inhibitory concentrations between 5 and 600nM and al...

journal_title：Bioorganic & medicinal chemistry

authors： Rice DR,de Lourdes Betancourt Mendiola M,Murillo-Solano C,Checkley LA,Ferdig MT,Pizarro JC,Smith BD

更新日期：2017-05-15 00:00:00

abstract：:Protein geranylgeranylation reactions are dependent on the availability of geranylgeranyl diphosphate (GGDP), which serves as the isoprenoid donor. Inhibition of GGDP synthase (GGDPS) is of interest from a drug development perspective as GGDPS inhibition results in impaired protein geranylgeranylation, which in multip...

journal_title：Bioorganic & medicinal chemistry

authors： Wills VS,Metzger JI,Allen C,Varney ML,Wiemer DF,Holstein SA

更新日期：2017-04-15 00:00:00

abstract：:A series of 2-substituted 6-t-butylpyridine and 4-t-butylphenyl C-region analogues of 2-(3-fluoro-4-methylsulfonamidophenyl)propanamides were investigated for hTRPV1 antagonism. The analysis of structure activity relationships indicated that the pyridine derivatives generally exhibited a little better antagonism than ...

journal_title：Bioorganic & medicinal chemistry

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

更新日期：2017-04-15 00:00:00

abstract：:Following our studies on structure-activity relationships of anti-rhinovirus chromene and chroman derivatives, we designed and synthesized new series of 3-phenylalkyl-2H-chromenes and -chromans bearing differently sized, aliphatic linker chains between the two cycles. The cytotoxicity and the antiviral activity of the...

journal_title：Bioorganic & medicinal chemistry

authors： Conti C,Proietti Monaco L,Desideri N

更新日期：2017-04-01 00:00:00

abstract：:Hormone sensitive lipase (HSL) has emerged as an attractive target for the treatment of dyslipidemia. We previously reported compound 1 as a potent and orally active HSL inhibitor. Although an attractive profile was demonstrated, subsequent studies revealed that compound 1 has a bioactivation liability. The oxygen-car...

journal_title：Bioorganic & medicinal chemistry

authors： Ogiyama T,Yamaguchi M,Kurikawa N,Honzumi S,Yamamoto Y,Sugiyama D,Takakusa H,Inoue SI

更新日期：2017-04-01 00:00:00

abstract：:We report here the synthesis of isoquebecol, an unprecedented constitutional isomer of quebecol, a polyphenolic compound discovered in maple syrup. The methodology used to prepare isoquebecol involves, as key steps, the formation of a dibromoalkene from an α-ketoester precursor, followed by a double Suzuki-Miyaura rea...

journal_title：Bioorganic & medicinal chemistry

authors： Cardinal S,Paquet-Côté PA,Azelmat J,Bouchard C,Grenier D,Voyer N

更新日期：2017-04-01 00:00:00

abstract：:Parasitic protozoa employ a salvage pathway to synthesize purines and generate essential active nucleotides, whereas mammals are capable of their de novo biosynthesis. This difference provides opportunity for the design of potential new antiprotozoan compounds. A series of 47 adenosine analogues was prepared with modi...

journal_title：Bioorganic & medicinal chemistry

authors： Tran HA,Zheng Z,Wen X,Manivannan S,Pastor A,Kaiser M,Brun R,Snyder FF,Back TG

更新日期：2017-04-01 00:00:00

abstract：:Cell division cycle 7 (Cdc7) is a serine/threonine kinase that plays important roles in the regulation of DNA replication process. A genetic study indicates that Cdc7 inhibition can induce selective tumor-cell death in a p53-dependent manner, suggesting that Cdc7 is an attractive target for the treatment of cancers. I...

journal_title：Bioorganic & medicinal chemistry

authors： Kurasawa O,Oguro Y,Miyazaki T,Homma M,Mori K,Iwai K,Hara H,Skene R,Hoffman I,Ohashi A,Yoshida S,Ishikawa T,Cho N

更新日期：2017-04-01 00:00:00

abstract：:The Wnt signaling pathway plays a key role in organ and tissue homeostasis, and when dysregulated, can become a major underlying mechanism of disease, particularly cancer. We reported previously that the anthelmintic drug Niclosamide inhibits Wnt/β-catenin signaling and suppresses colon cancer cell growth in vitro and...

journal_title：Bioorganic & medicinal chemistry

authors： Mook RA Jr,Ren XR,Wang J,Piao H,Barak LS,Kim Lyerly H,Chen W

更新日期：2017-03-15 00:00:00

abstract：:The piperazine ring of the potent nootropic drug DM235 has been decorated with H-bond donor and acceptor groups (CH2OH, CH2OMe, CH2OCOMe, COOEt); the aim was to insert new functional groups, suitable for further chemical manipulation. The influence of these modifications on nootropic activity was assessed by means of ...

journal_title：Bioorganic & medicinal chemistry

authors： Martino MV,Guandalini L,Di Cesare Mannelli L,Menicatti M,Bartolucci G,Dei S,Manetti D,Teodori E,Ghelardini C,Romanelli MN

更新日期：2017-03-15 00:00:00

abstract：:FIKKs are parasite-specific protein kinases with distinctive sequence motifs and their biological roles have not been completely elucidated. Here, we report the first potent Cryptosporidium FIKK (CpFIKK) inhibitor. We identified 4b as a potent (IC50=0.2nM) inhibitor of CpFIKK catalytic activity. In addition, we identi...

journal_title：Bioorganic & medicinal chemistry

authors： Osman KT,Ye J,Shi Z,Toker C,Lovato D,Jumani RS,Zuercher W,Huston CD,Edwards AM,Lautens M,Santhakumar V,Hui R

更新日期：2017-03-01 00:00:00

abstract：:Targeted polypharmacology provides an efficient method of treating diseases such as cancer with complex, multigenic causes provided that compounds with advantageous activity profiles can be discovered. Novel covalent TAK1 inhibitors were validated in cellular contexts for their ability to inhibit the TAK1 kinase and f...

journal_title：Bioorganic & medicinal chemistry

authors： Tan L,Gurbani D,Weisberg EL,Jones DS,Rao S,Singer WD,Bernard FM,Mowafy S,Jenney A,Du G,Nonami A,Griffin JD,Lauffenburger DA,Westover KD,Sorger PK,Gray NS

更新日期：2017-02-15 00:00:00

abstract：:A new series of 11-keto-β-boswellic acid and 3-O-acetyl-11-keto-β-boswellic acid analogs (5, 7, 8, 10, 13, 18a-d, 27a-c, 28a-d) were synthesized by modification of hydroxyl and acid functional moieties of boswellic acids. The structures of these analogs were confirmed by spectral data analysis (1H, 13C NMR and mass). ...

journal_title：Bioorganic & medicinal chemistry

authors： Meka B,Ravada SR,Murali Krishna Kumar M,Purna Nagasree K,Golakoti T

更新日期：2017-02-15 00:00:00

abstract：:Nrf2, which is a member of the cap'n'collar family of transcription factors, is a major regulator of phase II detoxification and anti-oxidant genes as well as anti-inflammatory and neuroprotective genes. The importance of inflammation and oxidative stress in many chronic diseases supports the concept that activation o...

journal_title：Bioorganic & medicinal chemistry

authors： Deck LM,Whalen LJ,Hunsaker LA,Royer RE,Vander Jagt DL

更新日期：2017-02-15 00:00:00

abstract：:Twelve optically pure enantiomers were obtained using either crystallization or chiral high performance liquid chromatography (HPLC) separation methodologies to resolve six racemic sigma-1 (σ1) receptor ligands. The in vitro binding affinities of each enantiomer for σ1, σ2 receptors and vesicular acetylcholine transpo...

journal_title：Bioorganic & medicinal chemistry

authors： Yue X,Jin H,Luo Z,Liu H,Zhang X,McSpadden ED,Tian L,Flores HP,Perlmutter JS,Parsons SM,Tu Z

更新日期：2017-02-15 00:00:00

abstract：:Synthesis and molecular validation of 6-substituted-2-(3-phenoxyphenyl)-4-phenylquinoline derivatives (4a-h) as antibacterial/DNA gyrase inhibitors reported. Primarily, 6-substituted-2-(3-phenoxyphenyl)-4-phenylquinoline derivatives were docked into the active sites of DNA gyrase A&B, to ensure the binding mode of the...

journal_title：Bioorganic & medicinal chemistry

authors： Alagumuthu M,Arumugam S

更新日期：2017-02-15 00:00:00

abstract：:A series of fifteen N4-benzyl substituted 5-nitroisatin-3-thiosemicarbazones 5a-o was synthesized and evaluated for urease inhibitory, phytotoxic and cytotoxic influences. All the compounds proved to be highly potent inhibitors of the enzyme, showing inhibitory activity (IC50=0.87±0.25-8.09±0.23μM) much better than th...

journal_title：Bioorganic & medicinal chemistry

authors： Pervez H,Khan N,Zaib S,Yaqub M,Naseer MM,Tahir MN,Iqbal J

更新日期：2017-02-01 00:00:00

abstract：:Methionine aminopeptidase (MetAP) is a class of ubiquitous enzymes essential for the survival of numerous bacterial species. These enzymes are responsible for the cleavage of N-terminal formyl-methionine initiators from nascent proteins to initiate post-translational modifications that are often essential to proper pr...

journal_title：Bioorganic & medicinal chemistry

authors： Helgren TR,Chen C,Wangtrakuldee P,Edwards TE,Staker BL,Abendroth J,Sankaran B,Housley NA,Myler PJ,Audia JP,Horn JR,Hagen TJ

更新日期：2017-02-01 00:00:00

abstract：:We have previously employed cyclization of a linear peptide as a strategy to modulate peptide function and properties, but cleavage to regenerate the linear peptide left parts of the linker structure on the peptide, interfering with its activity. Here, we focused on cyclization of a linear peptide via a "traceless" di...

journal_title：Bioorganic & medicinal chemistry

authors： Amano Y,Umezawa N,Sato S,Watanabe H,Umehara T,Higuchi T

更新日期：2017-02-01 00:00:00

abstract：:Selenium-incorporated fucoses (seleno-fucoses) differing in the position of the seleno-substituent were synthesized and applied to the X-ray structural determination of a carbohydrate-lectin complex using single/multi-wavelength anomalous dispersion (SAD/MAD) phasing. The hydroxyl groups at the C-1, -2, -3 and -4 posi...

journal_title：Bioorganic & medicinal chemistry

authors： Shimabukuro J,Makyio H,Suzuki T,Nishikawa Y,Kawasaki M,Imamura A,Ishida H,Ando H,Kato R,Kiso M

更新日期：2017-02-01 00:00:00

abstract：:Canavan disease is a fatal neurological disorder caused by defects in the metabolism of N-acetyl-l-aspartate (NAA). Recent work has shown that the devastating symptoms of this disorder are correlated with the elevated levels of NAA observed in these patients, caused as a consequence of the inability of mutated forms o...

journal_title：Bioorganic & medicinal chemistry

authors： Thangavelu B,Mutthamsetty V,Wang Q,Viola RE

更新日期：2017-02-01 00:00:00

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

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

abstract：:A series of twenty two (E)-N-cinnamoyl aminoalkanols derivatives monosubstituted in phenyl ring with 4-Cl, 4-CH3 or 2-CH3 was designed, synthesized and evaluated for anticonvulsant activity in rodent models of seizures: maximal electroshock (MES) test, subcutaneous pentylenetetrazole (scPTZ) test, and 6-Hz test. There...

journal_title：Bioorganic & medicinal chemistry

authors： Gunia-Krzyżak A,Żelaszczyk D,Rapacz A,Żesławska E,Waszkielewicz AM,Pańczyk K,Słoczyńska K,Pękala E,Nitek W,Filipek B,Marona H

更新日期：2017-01-15 00:00:00

abstract：:Vitamin D receptor (VDR) is a member of the nuclear receptor superfamily and regulates the expression of target genes through ligand binding. To express the target gene, coactivator binding to the VDR/ligand complex is essential. Although there are many coactivators in living cells, precise interactions between coacti...

journal_title：Bioorganic & medicinal chemistry

authors： Egawa D,Itoh T,Kato A,Kataoka S,Anami Y,Yamamoto K

更新日期：2017-01-15 00:00:00

abstract：:Recent accumulating evidence has supported the notion that tumors have hierarchically organized heterogeneous cell populations and a small subpopulation of cells, termed cancer stem cells (CSCs), are responsible for tumor initiation, maintenance as well as drug resistance. Therefore, targeting the CSCs along with the ...

journal_title：Bioorganic & medicinal chemistry

authors： Aztopal N,Karakas D,Cevatemre B,Ari F,Icsel C,Daidone MG,Ulukaya E

更新日期：2017-01-01 00:00:00

abstract：:Alzheimer's disease (AD) is characterized by the buildup of insoluble aggregated amyloid-β protein (Aβ) into plaques that accumulate between the neural cells in the brain. AD is the sixth leading cause of death in the United States and is the only cause of death among the top ten that cannot currently be treated or cu...

journal_title：Bioorganic & medicinal chemistry

authors： Turner JP,Chastain SE,Park D,Moss MA,Servoss SL

更新日期：2017-01-01 00:00:00

abstract：:Targeting Hsp90-Cdc37 protein-protein interaction (PPI) is becoming an alternative approach for future anti-cancer drug development. We previously reported the discovery of an eleven-residue peptide (Pep-1) with micromolar activity for the disruption of Hsp90-Cdc37 PPI. Efforts to improve upon the Pep-1 led to the dis...

journal_title：Bioorganic & medicinal chemistry

authors： Wang L,Li L,Fu WT,Jiang ZY,You QD,Xu XL

更新日期：2017-01-01 00:00:00

abstract：:The emergence of multidrug-resistant bacterial and fungal strains poses a threat to human health that requires the design and synthesis of new classes of antimicrobial agents. We evaluated bis(N-amidinohydrazones) and N-(amidino)-N'-aryl-bishydrazones for their antibacterial and antifungal activities against panels of...

journal_title：Bioorganic & medicinal chemistry

authors： Shrestha SK,Kril LM,Green KD,Kwiatkowski S,Sviripa VM,Nickell JR,Dwoskin LP,Watt DS,Garneau-Tsodikova S

更新日期：2017-01-01 00:00:00

abstract：:Vascular Adhesion Protein-1 (VAP-1) is a promising therapeutic target for the treatment of several inflammatory-related diseases including diabetic microvascular complication. We identified glycine amide derivative 3 as a novel structure with moderate VAP-1 inhibitory activity. Structure-activity relationship studies ...

journal_title：Bioorganic & medicinal chemistry

authors： Yamaki S,Suzuki D,Fujiyasu J,Neya M,Nagashima A,Kondo M,Akabane T,Kadono K,Moritomo A,Yoshihara K

更新日期：2017-01-01 00:00:00

abstract：:Janus kinases inhibitor is considered to have therapeutic potential for the treatment of oncology and immune-inflammatory diseases. Two series of 4-(2-benzofuranyl)pyrimidin-2-amine and 4-(4,5,6,7-tetrahydrofuro[3,2-c]pyridin-2-yl)pyrimidin-2-amine derivatives have been designed and synthesized. Primary SAR studies re...

journal_title：Bioorganic & medicinal chemistry

authors： Wang Y,Huang W,Xin M,Chen P,Gui L,Zhao X,Tang F,Wang J,Liu F

更新日期：2017-01-01 00:00:00

abstract：:The interaction of organic compounds with apoptosis regulatory proteins is an attractive field of research because of its relevance in the development of new chemotherapeutic agents for cancer treatment. Our group designed four new adamantane thiadiazole derivatives (ATDs). The four ATDs were theoretically tested for ...

journal_title：Bioorganic & medicinal chemistry

authors： Ali AG,Mohamed MF,Abdelhamid AO,Mohamed MS

更新日期：2017-01-01 00:00:00