Abstract：
:A public compound library with 260,000 compounds was screened virtually by computational docking for novel inhibitors of the transmembrane enzyme sarco/endoplasmic reticulum calcium ATPase (SERCA). Docking was performed with the program GOLD in conjunction with a high resolution X-ray crystal structure of SERCA. Compounds that were predicted to be active were tested in bioassays. Nineteen novel compounds were discovered that were capable of inhibiting the ATP hydrolysis activity of SERCA at concentrations below 50 microM. Crucial enzyme/inhibitor interactions were identified by analyzing the docking-predicted binding poses of active compounds. Like other SERCA inhibitors, the newly discovered compounds are of considerable medicinal interest because of their potential for cancer chemotherapy.
journal_name
Bioorg Med Chemjournal_title
Bioorganic & medicinal chemistryauthors
Deye J,Elam C,Lape M,Ratliff R,Evans K,Paula Sdoi
10.1016/j.bmc.2008.12.010subject
Has Abstractpub_date
2009-02-01 00:00:00pages
1353-60issue
3eissn
0968-0896issn
1464-3391pii
S0968-0896(08)01179-6journal_volume
17pub_type
杂志文章abstract：:Inhibition of Bcl-2 family protein-protein interactions (PPI) is a very promising direction in cancer chemotherapy. Hence over the last decade, many medicinal chemistry studies endeavoured to discover drug candidates, and a wealth of chemical scaffolds with striking chemical diversity was reported as Bcl-xL inhibitors...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2015.02.060
更新日期：2015-04-15 00:00:00
abstract：:A methanolic extract and its ethyl acetate-soluble fraction from Sri Lankan curry-leaf, the leaves of Murraya koenigii, inhibited melanogenesis in theophylline-stimulated murine B16 melanoma 4A5 cells. Two new carbazole alkaloids, karapinchamines A and B, were isolated from the ethyl acetate-soluble fraction together ...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2013.01.012
更新日期：2013-03-01 00:00:00
abstract：:We report a chiral switch in the configuration of 1-(p-methoxyphenyl)-propan-2-ol, synthesized in aqueous media by ketoreductase in the presence of high concentration of gamma-CD. NMR, ECD and fluorescence spectrometry were used in the effort to explain this unexpected effect. A comparison has been made between the ca...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2010.07.070
更新日期：2010-09-15 00:00:00
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
pub_type： 杂志文章
doi：10.1016/j.bmc.2018.10.001
更新日期：2018-11-01 00:00:00
abstract：:Aspartate-β-semialdehyde dehydrogenase (ASADH) lies at the first branch point in the aspartate metabolic pathway which leads to the biosynthesis of several essential amino acids and some important metabolites. This pathway is crucial for many metabolic processes in plants and microbes like bacteria and fungi, but is a...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2015.09.017
更新日期：2015-10-15 00:00:00
abstract：:A series of novel metronidazole aryloxy, carboxy and azole derivatives has been synthesized and their cytotoxic activities on three cancer cell lines were evaluated by MTT assay. Compounds 4m, 4l and 4d showed the most potent cytotoxic activity (IC50s less than 100 µg/mL). Apoptosis was also detected for these compoun...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2018.12.003
更新日期：2019-01-15 00:00:00
abstract：:1,2,4-Triazole and 1,3,4-oxadiazole analogues are of interest due to their potential activity against microbial and malarial infections. In search of suitable antimicrobial and antimalarial compounds, we report here the synthesis, characterization and biological activities of 1,2,4-triazole and 1,3,4-oxadiazole analog...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2017.05.054
更新日期：2017-08-01 00:00:00
abstract：:Tankyrases-1 and -2 (TNKS-1 and TNKS-2) have three cellular roles which make them important targets in cancer. Using NAD(+) as a substrate, they poly(ADP-ribosyl)ate TRF1 (regulating lengths of telomeres), NuMA (facilitating mitosis) and axin (in wnt/β-catenin signalling). Using molecular modelling and the structure o...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2015.06.061
更新日期：2015-09-01 00:00:00
abstract：:The present quantitative structure-activity relationship (QSAR) study attempts to explore the structural and physicochemical requirements of mannitol derivatives for HIV protease inhibitory activity using linear free energy related model of Hansch. QSAR models have been developed using electronic (Hammett sigma), hydr...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2005.09.022
更新日期：2006-02-15 00:00:00
abstract：:Although many compounds have been approved for the treatment of human immunodeficiency type-1 (HIV-1) infection, additional anti-HIV-1 drugs (particularly those belonging to new drug classes) are still needed due to issues such as long-term drug-associated toxicities, transmission of drug-resistant variants, and devel...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2016.03.052
更新日期：2016-06-01 00:00:00
abstract：:It is well established that tobacco smokers have reduced levels of monoamine oxidase activities both in the brain and peripheral organs. Furthermore, extensive evidence suggests that smokers are less prone to develop Parkinson's disease. These facts, plus the observation that inhibition of monoamine oxidase B protects...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2005.12.057
更新日期：2006-05-15 00:00:00
abstract：:Thirty-one 3-aryl-4-alkylaminofuran-2(5H)-ones were designed, prepared and tested for their antibacterial activity. Some of them showed significant antibacterial activity against Gram-positive organisms, especially against Staphylococcus aureus ATCC 25923, but all were inactive against Gram-negative organisms. Out of ...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2011.01.051
更新日期：2011-03-01 00:00:00
abstract：:Nuclear monoamination of a 1,4-naphthohydroquinone with primary aromatic amines was catalysed by the commercial laccase, Novozym 51003, from Novozymes to afford aminonaphthoquinones. The synthesis was accomplished by reacting a mixture of the primary amine and 1,4-naphthohydroquinone in succinate-lactate buffer and a ...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2012.05.028
更新日期：2012-07-15 00:00:00
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journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2012.09.032
更新日期：2012-11-15 00:00:00
abstract：:Mycobacterium tuberculosis (M.Tb) is a bacillus capable of causing a chronic and fatal condition in humans known as tuberculosis (TB). It is estimated that there are 8 million new cases of TB per year and 3.1 million infected people die annually. Thirty-six new amide quinoxaline 1,4-di-N-oxide derivatives have been sy...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2010.02.024
更新日期：2010-04-01 00:00:00
abstract：:Various 4-analogues of podophyllotoxin and epipodophyllotoxin were obtained via the formation of the corresponding 4-keto derivatives. Methyloximation of podophyllotoxone, followed by subsequent catalytic hydrogenation, gave stereoselective access to 4-alpha-amino-4-deoxypodophyllotoxin and from there, to the correspo...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/s0968-0896(02)00255-9
更新日期：2002-11-01 00:00:00
abstract：:Heroin is a highly abused opioid that has reached epidemic status within the United States. Yet, existing therapies to treat addiction are inadequate and frequently result into rates of high recidivism. Vaccination against heroin offers a promising alternative therapeutic option but requires further development to enh...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2018.11.027
更新日期：2019-01-01 00:00:00
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journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2007.06.033
更新日期：2007-09-15 00:00:00
abstract：:The benzamidine moiety, a well-known arginine mimetic, has been introduced in a variety of ligands, including peptidomimetic inhibitors of trypsin-like serine proteases. According to their primary substrate specificity, the benzamidine residue interacts with the negatively charged aspartate at the bottom of the S1 poc...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2012.08.042
更新日期：2012-11-01 00:00:00
abstract：:A series of 1-substituted-3(5)-(6-methylpyridin-2-yl)-4-(quinolin-6-yl)pyrazoles 14a-e, 15a-e, 17a-c, and 18a-d have been synthesized and evaluated for their ALK5 inhibitory activity in an enzyme assay and in a cell-based luciferase reporter assay. The 6-quinolinyl pyrazole analogue 14b inhibited ALK5 phosphorylation ...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2011.03.008
更新日期：2011-04-15 00:00:00
abstract：:Non-nucleoside reverse transcriptase inhibitors (NNRTIs) represent an integral part of the currently available combination antiretroviral therapy (cART) contributing to reduce the AIDS-mortality and turned the disease from lethal to chronic. In this context we recently reported a series of 6-chloro-1-(3-methylphenylsu...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2017.05.040
更新日期：2017-07-15 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
pub_type： 杂志文章
doi：10.1016/j.bmc.2016.10.011
更新日期：2017-01-01 00:00:00
abstract：:We have developed a method for the chemoselective introduction of spacer modified biotin labels into unprotected multi-functional amines. A range of novel biotin spacer conjugates attached to a polymer-bound sulfonamide anchor was prepared using established amide bond forming procedures. After chemical transformation ...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2004.03.038
更新日期：2004-06-01 00:00:00
abstract：:Three haloderivatives of noscapine 2-4 were synthesized chemoselectively and their in vitro cytotoxicity was assessed by MTT assay on U-87 human glioblastoma cell lines. At 50 microM concentration after 72 h, 9-chloronoscapine 2, 9-bromonoscapine 3 (EM011), and 9-iodonoscapine 4 killed 87.8%, 51.2%, and 56.8% cells, r...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2006.05.069
更新日期：2006-10-01 00:00:00
abstract：:A quantitative structure-activity analysis of binding affinity of a series of 30 steroids for corticosteroid-binding globulin was performed using Wang-Ford charges of the non-hydrogen common atoms obtained from molecular electrostatic potential surface of AM1 optimized energy-minimized geometries of the compounds. Att...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2004.03.055
更新日期：2004-06-15 00:00:00
abstract：:We examined the properties of RNA analogues containing 2'-deoxy-2'-alpha-fluorouridine (1) or 2'-O-methyluridine (2) as inhibitors against human RNase L, that cleaves a single-stranded RNA in the presence of 2',5'-linked oligoadenylate (2-5A). The RNA analogue, FF, containing two molecules of 1 in place of uridine eff...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2003.08.025
更新日期：2003-11-17 00:00:00
abstract：:Semiempirical quantum mechanical and molecular mechanics calculations were carried out to identify and characterize the steric and electronic properties that modulate ligand recognition and activation of the cerebellar GABAA/benzodiazepine (BDZ) receptor. For this hypothesis development, thirteen compounds belonging t...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/s0968-0896(00)82053-2
更新日期：1994-10-01 00:00:00
abstract：:The dysfunction and mutual compensatory activation of RAF-MEK-ERK and PI3K-PDK1-AKT pathways have been demonstrated as the hallmarks in several primary and recurrent cancers. The strategy of concurrent blocking of these two pathways shows clinical merits on effective cancer therapy, such as combinatory treatments and ...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2019.01.028
更新日期：2019-03-15 00:00:00
abstract：:Accumulation and deposition of misfolded amyloid β (Aβ) peptide outside the nerve cells are one of the major causes of Alzheimer's disease (AD). To date, one of the promising therapeutic strategies for AD is to block the early steps associated with the aggregation of Aβ peptide. We have developed synthetic breaker pep...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2021.116017
更新日期：2021-01-16 00:00:00
abstract：:A series of potential substrates of gamma-aminobutyric acid aminotransferase (GABA-AT) with lipophilic bioisosteres of the carboxylic acid group (2-7) were synthesized and tested. Most of the synthesized compounds showed substrate activities with GABA-AT; 1H-tetrazole-5-propanamine (6) was the best of those tested. Th...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2005.09.067
更新日期：2006-03-01 00:00:00
