abstract：:The glutamine transporter ASCT2 has been identified as a promising target to inhibit rapid growth of cancer cells. However, ASCT2 pharmacology is not well established. In this report, we performed a systematic structure activity analysis of a series of substituted benzylproline derivatives. Substitutions on the phenyl...

journal_title：Bioorganic & medicinal chemistry letters

authors： Singh K,Tanui R,Gameiro A,Eisenberg G,Colas C,Schlessinger A,Grewer C

更新日期：2017-02-01 00:00:00

abstract：:Human kallikrein 1 (KLK1) is the most extensively studied member of this family and plays a major role in inflammation processes. From Ugi multicomponent reactions, isomannide-based peptidomimetic 10 and 13 where synthesized and showed low micromolar values of IC50 for KLK1 The most active compound (10) presented comp...

journal_title：Bioorganic & medicinal chemistry letters

authors： Barros TG,Santos JAN,de Souza BEG,Sodero ACR,de Souza AMT,da Silva DP,Rodrigues CR,Pinheiro S,Dias LRS,Abrahim-Vieira B,Puzer L,Muri EMF

更新日期：2017-01-15 00:00:00

abstract：:The expression of epidermal growth factor receptor (EGFR) across a wide range of tumor cells has attracted attention for use as a tumor marker in drug delivery systems. Therefore, binding molecules with the ability to target EGFR have been developed. Among them, we focused on affibodies that are binding proteins deriv...

journal_title：Bioorganic & medicinal chemistry letters

authors： Nishimura Y,Ezawa R,Ishii J,Ogino C,Kondo A

更新日期：2017-01-15 00:00:00

abstract：:Vitamin K is the collective term for compounds that share a 2-methyl-1,4-naphthoquinone ring, but differ in the side-chain at the 3-position. We synthesized novel 2-methyl-1,4-naphthoquinone derivatives with different side chain length at the 3-position. Derivatives with C-14 and C-16 tails showed the highest in vitro...

journal_title：Bioorganic & medicinal chemistry letters

authors： Vermeer C,van 't Hoofd C,Knapen MHJ,Xanthoulea S

更新日期：2017-01-15 00:00:00

abstract：:Elevated triglycerides (TG) contribute towards increased risk for cardiovascular disease. Lipoprotein lipase (LPL) is an enzyme that is responsible for the metabolism of core triglycerides of very-low density lipoproteins (VLDL) and chylomicrons in the vasculature. In this study, we explored the structure-activity rel...

journal_title：Bioorganic & medicinal chemistry letters

authors： Geldenhuys WJ,Caporoso J,Leeper TC,Lee YK,Lin L,Darvesh AS,Sadana P

更新日期：2017-01-15 00:00:00

abstract：:Activity-based probes are small molecules that covalently bind to the active site of a protease in an activity-dependent manner. We synthesized and characterized two fluorescent activity-based probes that target serine proteases with trypsin-like or elastase-like activity. We assessed the selectivity and potency of th...

journal_title：Bioorganic & medicinal chemistry letters

authors： Edgington-Mitchell LE,Barlow N,Aurelio L,Samha A,Szabo M,Graham B,Bunnett N

更新日期：2017-01-15 00:00:00

abstract：:S1P receptors (S1PR1-5) are a group of GPCRs activated by a high affinity binding with S1P that have important roles in the regulation of the immune system. A potent S1PR agonist FTY720 is an immunomodulator used to treat multiple sclerosis and several 'second generation' drugs are under clinical development. Subtype-...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hur W,Rosen H,Gray NS

更新日期：2017-01-01 00:00:00

abstract：:Five new p-terphenyls named prenylterphenyllin D (1), prenylterphenyllin E (2), 2'-O-methylprenylterphenyllin (3), 4-O-methylprenylterphenyllin (4) and 3'-O-methylterphenyllin (5) together with seven known compounds (6-12), were isolated from cultures of Aspergillus sp. YXf3. The structures of the new compounds were e...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yan W,Wuringege,Li SJ,Guo ZK,Zhang WJ,Wei W,Tan RX,Jiao RH

更新日期：2017-01-01 00:00:00

abstract：:Three new polyhydroxytriterpenoid derivatives, 23-O-neochebuloylarjungenin 28-O-β-d-glycopyranosyl ester (1), 23-O-4'-epi-neochebuloylarjungenin (2), and 23-O-galloylpinfaenoic acid 28-O-β-d-glucopyranosyl ester (17) were isolated from the fruits of Terminalia chebula Retz. along with fourteen known ones. Their struct...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lee DY,Yang H,Kim HW,Sung SH

更新日期：2017-01-01 00:00:00

abstract：:The Keap1-Nrf2 system is involved not only in biological defense but also in malignancy progression and chemoresistance. The ubiquitin-binding protein p62/Sqstm1 (p62), which is highly expressed in several cancers, competes with Nrf2 for Keap1 binding, leading to activation of Nrf2-mediated gene expression and surviva...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yasuda D,Nakajima M,Yuasa A,Obata R,Takahashi K,Ohe T,Ichimura Y,Komatsu M,Yamamoto M,Imamura R,Kojima H,Okabe T,Nagano T,Mashino T

更新日期：2016-12-15 00:00:00

abstract：:Novel approaches that do not rely upon developing microbicidal compounds are sorely needed to combat multidrug resistant (MDR) bacteria. The potential of marine secondary metabolites to serve as a source of non-traditional anti-bacterial agents is demonstrated by showing that pyrrole-imidazole alkaloids inhibit biofil...

journal_title：Bioorganic & medicinal chemistry letters

authors： Melander RJ,Liu HB,Stephens MD,Bewley CA,Melander C

更新日期：2016-12-15 00:00:00

abstract：:While a correlation between blockade of the orexin 2 receptor (OX2R) with either a dual orexin receptor antagonist (DORA) or a selective orexin 2 receptor antagonist (2-SORA) and a decrease of wakefulness is well established, less is known about selective blockade of the orexin 1 receptor (OX1R). Therefore, a highly s...

journal_title：Bioorganic & medicinal chemistry letters

authors： Stump CA,Cooke AJ,Bruno J,Cabalu TD,Gotter AL,Harell CM,Kuduk SD,McDonald TP,O'Brien J,Renger JJ,Williams PD,Winrow CJ,Coleman PJ

更新日期：2016-12-01 00:00:00

abstract：:Natural or synthetic coumarins showed gastroprotective and antiulcer activity in animal models. In this study, we have synthetized twenty coumarins using classic methods to evaluate their gastroprotective effects on the ethanol/HCl-induced gastric lesion model in mice at 20mg/kg. Among the coumarins synthetized, compo...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sepulveda B,Quispe C,Simirgiotis M,Torres-Benítez A,Reyes-Ortíz J,Areche C,García-Beltrán O

更新日期：2016-12-01 00:00:00

abstract：:EPR oximetry with the use of trityl radicals can enable sensitive O2 measurement in biological cells and tissues. However, in vitro cellular and in vivo biological applications are limited by rapid trityl probe degradation or biological clearance and the need to enhance probe O2 sensitivity. We synthesized novel perfl...

journal_title：Bioorganic & medicinal chemistry letters

authors： Dhimitruka I,Alzarie YA,Hemann C,Samouilov A,Zweier JL

更新日期：2016-12-01 00:00:00

abstract：:Glycogen synthase kinase-3 beta (GSK3β) kinase serves as a promising therapeutic target for the treatment of various human diseases, such as diabetes, obesity, and Alzheimer's disease. In this study, we report lead GSK3β inhibitors identified using a fragment-linking strategy. Through the systematic exploration, a six...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kim J,Moon Y,Hong S

更新日期：2016-12-01 00:00:00

abstract：:To continue our study of 2-morpholino-benzoxazine based compounds, which show useful activity against PI3K family enzymes or antiplatelet activity, we designed and synthesized a series of linear 6.7-fused, 5,6-angular fused and 7,8-angular fused-aryl-morpholino-naphth-oxazines. The compounds were prepared from substit...

journal_title：Bioorganic & medicinal chemistry letters

authors： Morrison R,Zheng Z,Jennings IG,Thompson PE,Al-Rawi JMA

更新日期：2016-11-15 00:00:00

abstract：:A novel class of mesoionic pyrido[1,2-a]pyrimidinones has been discovered with exceptional insecticidal activity controlling a number of insect species, particularly hemiptera and lepidoptera. Mode-of-action studies showed that they act on nicotinic acetylcholine receptors (nAChRs) primarily as inhibitors. Here we rep...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zhang W,Holyoke CW Jr,Barry J,Leighty RM,Cordova D,Vincent DR,Hughes KA,Tong MT,McCann SF,Xu M,Briddell TA,Pahutski TF,Lahm GP

更新日期：2016-11-15 00:00:00

abstract：:Compound DNSTT-Cu2+, a novel chelate of Cu2+ with DOTA conjugated to a fluorescent dansyl fragment, is developed for imaging cell apoptosis. Apoptotic U-87MG cells could be selectively visualized by the fluorescence of DNSTT-Cu2+ from cytoplasm of cells, confirmed by the fluorescence of apoptosis cells co-labeled with...

journal_title：Bioorganic & medicinal chemistry letters

authors： Han J,Wang X,Yu M

更新日期：2016-11-15 00:00:00

abstract：:Using molecular modeling and rationally designed structural modifications, the multi-target structure-activity relationship for a series of ranitidine analogs has been investigated. Incorporation of a variety of isosteric groups indicated that appropriate aromatic moieties provide optimal interactions with the hydroph...

journal_title：Bioorganic & medicinal chemistry letters

authors： Gao J,Midde N,Zhu J,Terry AV,McInnes C,Chapman JM

更新日期：2016-11-15 00:00:00

abstract：:Amyloid-β (Aβ) deposition and oxidative stress observed in the brains of patients with Alzheimer's disease (AD) are important targets for therapeutic intervention. In this study, we conjugated the antioxidants caffeic acid (CA) and dihydrocaffeic acid (DHCA) to Aβ1-42 C-terminal motifs (Aβx-42: x=38, 40) to synthesize...

journal_title：Bioorganic & medicinal chemistry letters

authors： Arai T,Ohno A,Mori K,Kuwata H,Mizuno M,Imai K,Hara S,Shibanuma M,Kurihara M,Miyata N,Nakagawa H,Fukuhara K

更新日期：2016-11-15 00:00:00

abstract：:The formation of blood clots in blood vessels causes severe ischemic diseases such as cerebral infarction and myocardial infarction. While searching for microbial products that increase fibrinolytic activity using an in vitro fibrin degradation assay, we found malformin A1, a disulfide form of cyclo(-d-Cys-d-Cys-l-Val...

journal_title：Bioorganic & medicinal chemistry letters

authors： Koizumi Y,Nagai K,Hasumi K,Kuba K,Sugiyama T

更新日期：2016-11-01 00:00:00

abstract：:With the aim of finding more potential inhibitors against NADH-fumarate reductase (specific target for treating helminthiasis and cancer) from natural resources, Talaromyces wortmannii was treated with the epigenome regulatory agent suberoylanilide hydroxamic acid, which resulted in the isolation of four new wortmanni...

journal_title：Bioorganic & medicinal chemistry letters

authors： Liu WC,Wang YY,Liu JH,Ke AB,Zheng ZH,Lu XH,Luan YS,Xiu ZL,Dong YS

更新日期：2016-11-01 00:00:00

abstract：:Hypoxia is a characteristic feature of solid tumors. Herein, we have developed novel hypoxia-sensitive probes (IM-ACs) for Raman spectroscopic analysis, consisting of nitroimidazole as a hypoxia-targeting unit and acetylene group as the signal-emitting unit. Among IM-ACs synthesized in this study, IM-AC possessing a d...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kurihara R,Ikemura Y,Tanabe K

更新日期：2016-10-15 00:00:00

abstract：:The peptidomimetic, LLP2A, is a specific, high-affinity ligand for α4β1 integrin receptors. Previously, several PEGylated LLP2A conjugates were evaluated in vivo as imaging agents for the detection of lymphoma, leukemia, multiple myeloma and melanoma tumours via NIR-fluorescence, 111In-SPECT, and 64Cu- and 68Ga-PET im...

journal_title：Bioorganic & medicinal chemistry letters

authors： Walker D,Li Y,Roxin Á,Schaffer P,Adam MJ,Perrin DM

更新日期：2016-10-15 00:00:00

abstract：:Large neutral amino acid transporter 1 (LAT1) is a solute carrier protein located primarily in the blood-brain barrier (BBB) that offers the potential to deliver drugs to the brain. It is also up-regulated in cancer cells, as part of a tumor's increased metabolic demands. Previously, amino acid prodrugs have been show...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zur AA,Chien HC,Augustyn E,Flint A,Heeren N,Finke K,Hernandez C,Hansen L,Miller S,Lin L,Giacomini KM,Colas C,Schlessinger A,Thomas AA

更新日期：2016-10-15 00:00:00

abstract：:Developing targeted validation probes that can interrogate biology is of interest for both chemists and biologists. The synthesis of suitable compounds provides a means for avoiding the costly labeling of cells with specific antibodies and the bias associated with the interpretation of biological validation experiment...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ho LA,Thomas E,McLaughlin RA,Flematti GR,Fuller RO

更新日期：2016-10-15 00:00:00

abstract：:Cyanobacteria possess a unique capacity for the production of structurally novel secondary metabolites compared to the biosynthetic abilities of other environmental prokaryotes such as bacteria of the genus Streptomyces. Two different strategies to explore cyanobacteria-derived natural products have been explored prev...

journal_title：Bioorganic & medicinal chemistry letters

authors： Harms H,Kurita KL,Pan L,Wahome PG,He H,Kinghorn AD,Carter GT,Linington RG

更新日期：2016-10-15 00:00:00

abstract：:Exogenous short-chain nucleic acids undergo rapid import into the nucleus. Fluorescence-labeled dT1-13 DNA microinjected into the cytoplasm domain of a HeLa cell was rapidly imported into the nucleus domain within 1min. This is much more rapid than what has been observed for intracellular diffusion of small molecules....

journal_title：Bioorganic & medicinal chemistry letters

authors： Kitagawa M,Okamoto A

更新日期：2016-10-01 00:00:00

abstract：:In vitro metabolic identification studies with a PI3K-α inhibitor lead molecule 1 identified a single predominant site of oxidative metabolism to be occurring within a tert.butyl moiety. Modification of the tert.butyl group within the lead molecule 1, to the corresponding d9-tert.butyl analogue 2, led to an increase i...

journal_title：Bioorganic & medicinal chemistry letters

authors： Fairhurst RA,Caravatti G,Guagnano V,Aichholz R,Blanz J,Blasco F,Wipfli P,Fritsch C,Maira SM,Schnell C,Seiler FH

更新日期：2016-10-01 00:00:00

abstract：:Strontium fructose 1,6-diphosphate (FDP-Sr) is a new strontium-containing compound. The primary aim of this study was to clarify whether the structure component of FDP-Sr, FDP could benefit the protective effect of Sr (II) against oxidative stress induced apoptosis, and meanwhile to further explore the important role ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Qi HH,Bao J,Zhang Q,Ma B,Gu GY,Zhang PL,Ou-Yang G,Wu ZM,Ying HJ,Ou-Yang PK

更新日期：2016-10-01 00:00:00

abstract：:Mismatch binding protein MutS binding to bulge structure in DNA duplexes was controlled by UV irradiation. 4-O-(2-Nitrobenzyl)thymidine or 4-O-[2-(2-nitrophenyl)propyl]thymidine was incorporated into DNA duplexes a bulged position. The MutS did not bind to the caged DNA duplexes but bound after removing the 2-nitroben...

journal_title：Bioorganic & medicinal chemistry letters

authors： Seio K,Ohno Y,Ohno K,Takeshita L,Kanamori T,Masaki Y,Sekine M

更新日期：2016-10-01 00:00:00

abstract：:Two series of novel tricyclic oxazine and oxazepine fused quinazolines have been designed and synthesized. The in vitro antitumor effect of the title compounds was screened on N87, A431, H1975, BT474 and Calu-3 cell lines. Compared to gefitinib and erlotinib, compounds 1a-1h were found to demonstrate more potent antit...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sun M,Zhao J,Chen X,Zong Z,Han J,Du Y,Sun H,Wang F

更新日期：2016-10-01 00:00:00

abstract：:2-Propargylthiobenzimidazole 1, 4-bromomethyl coumarins/1-aza-coumarins 2/3 and sodium azide have been reacted in one pot under Click chemistry conditions to give exclusively 1,4-disubstituted triazoles 5a-n. Anti-tubercular assays against M. tuberculosis (H37Rv) coupled with in silico molecular docking studies indica...

journal_title：Bioorganic & medicinal chemistry letters

authors： Anand A,Kulkarni MV,Joshi SD,Dixit SR

更新日期：2016-10-01 00:00:00

abstract：:A series of colchicine site binding tubulin inhibitors were designed and synthesized by the modification of the combretastatin A-4 (CA4) pharmacophore. The ring B was replaced by the pharmacologically relevant benzimidazole or benzothiazole scaffolds, and the cis-configuration of the olefinic bond was restricted by th...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ashraf M,Shaik TB,Malik MS,Syed R,Mallipeddi PL,Vardhan MVPSV,Kamal A

更新日期：2016-09-15 00:00:00

abstract：:Existing CB1 negative allosteric modulators (NAMs) fall into a limited range of structural classes. In spite of the theoretical potential of CB1 NAMs, published in vivo studies have generally not been able to demonstrate the expected therapeutically-relevant CB1-mediated effects. Thus, a greater range of molecular too...

journal_title：Bioorganic & medicinal chemistry letters

authors： Greig IR,Baillie GL,Abdelrahman M,Trembleau L,Ross RA

更新日期：2016-09-15 00:00:00

abstract：:A fluorescent sensor based on a tripeptide (SerGluGlu) with a dansyl fluorophore detected selectively Al(III) among 16 metal ions in aqueous buffered solutions without any organic cosolvent. The peptide-based sensor showed a highly sensitive turn on response to aluminium ion with high binding affinity (1.84×10(4)M(-1)...

journal_title：Bioorganic & medicinal chemistry letters

authors： In B,Hwang GW,Lee KH

更新日期：2016-09-15 00:00:00

abstract：:Protein conjugation with ubiquitin and ubiquitin-like small molecules, such as UFM1, is important for promoting cancer cell survival and proliferation. Herein, the development of the first selective micromolar inhibitor of the UBA5 E1 enzyme that initiates UFM1 protein conjugation is described. This organometallic inh...

journal_title：Bioorganic & medicinal chemistry letters

authors： da Silva SR,Paiva SL,Bancerz M,Geletu M,Lewis AM,Chen J,Cai Y,Lukkarila JL,Li H,Gunning PT

更新日期：2016-09-15 00:00:00

abstract：:In the catalytic core of 10-23 DNAzyme, its five adenine residues are moderate conservative, but with highly conserved functional groups like 6-amino group and 7-nitrogen atom. It is this critical conservation that these two groups could be modified for better contribution. With 2'-deoxyadenosine analogues, several fu...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zhu J,Li Z,Wang Q,Liu Y,He J

更新日期：2016-09-15 00:00:00

abstract：:To develop potent chemotherapeutic agents for treating colorectal cancers, polymethoxylated 3-naphthyl-5-phenylpyrazoline-carbothioamide derivatives were designed. Twenty-two novel derivatives were synthesized and their cytotoxicities were measured using a clonogenic long-term survival assay. Of these derivatives, 3-(...

journal_title：Bioorganic & medicinal chemistry letters

authors： Shin SY,Ahn S,Yoon H,Jung H,Jung Y,Koh D,Lee YH,Lim Y

更新日期：2016-09-01 00:00:00

abstract：:IRAK4 has been identified as potential therapeutic target for inflammatory and autoimmune diseases. Herein we report the identification and initial SAR studies of a new class of pyrazole containing IRAK4 inhibitors designed to expand chemical diversity and improve off target activity of a previously identified series....

journal_title：Bioorganic & medicinal chemistry letters

authors： Hanisak J,Seganish WM,McElroy WT,Tang H,Zhang R,Tsui HC,Fischmann T,Tulshian D,Tata J,Sondey C,Devito K,Fossetta J,Garlisi CG,Lundell D,Niu X

更新日期：2016-09-01 00:00:00