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 moieties of this structural class. These studies have revealed the importance of functionalization of the carbohydrate hydroxy groups with both acetylated and methylated analogues showing increased potency relative to those with unsubstituted sugar moieties. In addition, the requirement for the presence and position of the C-ring lactone has been demonstrated through reduction and selective re-oxidation of the lactone ring. The most potent compound in this study displayed an IC50 value of 18 nM in an HT-29 assay with several others ranging from 50 to 200 nM. In an effort to elucidate their potential mechanism(s) of action, the DNA topoisomerase IIa inhibitory activity of the most potent compounds was examined based on previous reports of structurally similar compounds, but does not appear to contribute significantly to their antiproliferative effects.
journal_name
Bioorg Med Chemjournal_title
Bioorganic & medicinal chemistryauthors
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 JRdoi
10.1016/j.bmc.2018.03.033subject
Has Abstractpub_date
2018-05-15 00:00:00pages
2354-2364issue
9eissn
0968-0896issn
1464-3391pii
S0968-0896(17)32459-8journal_volume
26pub_type
杂志文章abstract：:Herpes Simplex Virus (HSV) infections are among the most common human diseases. In this work, we assess the structural features and electronic properties of a series of ten 1-hydroxyacridone derivatives (1a-j) recently described as a new class of non-nucleoside inhibitors of Herpes Simplex Virus-1 (HSV-1). Based on th...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2007.09.032
更新日期：2008-01-01 00:00:00
abstract：:The design, synthesis, and evaluation of a series of novel inhibitors of aspartate transcarbamoylase (ATCase) are reported. Several submicromolar phosphorus-containing inhibitors are described, but all-carboxylate compounds are inactive. Compounds were synthesized to probe the postulated cyclic transition-state of the...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2009.09.045
更新日期：2009-11-15 00:00:00
abstract：:A series of novel cinnamic acyl sulfonamide derivatives (9a-16e) have been designed and synthesized and their biological activities were also evaluated as potential tubulin polymerization inhibitors. Among all the compounds, 10c showed the most potent growth inhibitory activity against B16-F10 cancer cell line in vitr...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2011.06.088
更新日期：2011-08-15 00:00:00
abstract：:Posttranslational modification of proteins with ubiquitin and ubiquitin-like modifiers such as SUMO can be reverted by specific proteases, also referred to as deubiquitinases and isopeptidases, most of which are cysteine-dependent. We have found that the replacement of the conserved C-terminal glycine with propargylam...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2013.02.039
更新日期：2013-05-01 00:00:00
abstract：:Cyclopentane derivatives, designated as BCX-1812, BCX-1827, BCX-1898, and BCX-1923, were tested in parallel with oseltamivir carboxylate and zanamivir for the in vivo activity in mice infected with A/Turkey/Mas/76 X A/Beijing/32/92 (H6N2) influenza virus. The compounds were tested orally and intranasally at different ...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2005.03.048
更新日期：2005-06-02 00:00:00
abstract：:A series of novel combretastatin-A4 analogues in which the cis-olefinic bridge is replaced by an imidazolone-amide were synthesized, and their cytotoxicity and tubulin-polymerization inhibitory activities were evaluated. These compounds appear to be potential tubulin-polymerization inhibitors. Compounds 10, 9b and 9c,...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2011.03.068
更新日期：2011-06-01 00:00:00
abstract：:The synthesis of new meridianin derivatives substituted at the C-5 position of the 2-aminopyrimidine ring by various aryl groups and substituted or not by a methyl group on the indole nitrogen is described. These compounds were tested for their kinase inhibitory potencies toward five kinases (CDK5/p25, CK1delta/epsilo...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2009.05.017
更新日期：2009-07-01 00:00:00
abstract：:A series of heteroaryl-pyridine containing inhibitors of Akt are reported. The synthesis and structure-activity relationships are discussed, leading to the discovery of a indazole-pyridine analogue (K(i)=0.16 nM). These compounds bind in the ATP binding site, are potent, ATP competitive, and reversible inhibitors of A...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2006.06.047
更新日期：2006-10-15 00:00:00
abstract：:P2X4 receptor has become an interesting molecular target for treatment and PET imaging of neuroinflammation and associated brain diseases such as Alzheimer's disease. This study reports the first design, synthesis, radiolabeling and biological evaluation of new candidate PET P2X4 receptor radioligands using 5-BDBD, a ...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2017.05.031
更新日期：2017-07-15 00:00:00
abstract：:Pharmacological suppression of leukotriene biosynthesis by 5-lipoxygenase (5-LO)-activating protein (FLAP) inhibitors is a promising strategy to intervene with inflammatory, allergic and cardiovascular diseases. Virtual screening targeting FLAP based on a combined ligand- and structure-based pharmacophore model led to...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2012.04.048
更新日期：2012-06-15 00:00:00
abstract：:Combretastatin A-4 (CA-4) is a highly cytotoxic natural product and several derivatives have been prepared which underwent clinical trial. These investigations revealed that the cis-stilbene moiety of the natural product is prone to undergo cis/trans isomerization under physiological conditions, reducing the overall a...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2019.07.048
更新日期：2019-10-01 00:00:00
abstract：:New acridine derivatives bearing two symmetrical imidazolidinone rings, 3,6-bis((1-alkyl-5-oxo-imidazolidin-2-yliden)imino)acridine hydrochlorides 6a-6e (alkyl=ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl), have been prepared and their interactions with calf thymus DNA and selected cell lines were studied. The DNA-bind...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2011.01.012
更新日期：2011-03-01 00:00:00
abstract：:Formation of dinitrosyl iron complexes (DNICs) was observed in a wide spectrum of pathophysiological conditions associated with overproduction of NO. To gain insight into the possible genotoxic effects of DNIC, we examined the interaction of histidinyl dinitrosyl iron complexes (HIS-DNIC) with DNA by means of circular...
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：:Eurycomanone (1) and 13β,21-epoxyeurycomanone (2) were isolated from Eurycoma longifolia for studies of lipolytic activity. Compound 1 enhanced lipolysis in adipocytes with an EC50 of 14.6μM, while its epoxy derivate, compound 2, had a stronger activity with an EC50 of 8.6μM. Based on molecular mechanistic study using...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2017.07.032
更新日期：2017-09-01 00:00:00
abstract：:Ionophoric properties of dipyrazolic crowns and podands containing a 1,3-bis(1H-pyrazol-1-yl)propane unit in their structure are described. They show selectivity of ammonium vs alkali cations and interesting norepinephrine transport rates. A molecular modelling study has been used to elucidate the superstructures of t...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/s0968-0896(96)00250-7
更新日期：1997-02-01 00:00:00
abstract：:An efficient and practical strategy for the synthesis of (3R,4s,5S)-4-(2-hydroxyethyl) piperidine-3,4,5-triol and its N-alkyl derivatives 8a-f, starting from the D-glucose, is reported. The chiral pool methodology involves preparation of the C-3-allyl-α-D-ribofuranodialdose 10, which was converted to the C-5-amino der...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2014.09.034
更新日期：2014-11-01 00:00:00
abstract：:A series of 3- and 4-(sulfo- and sulfonamidoalkyl)pyridine and piperidine-2-carboxylic acid derivatives as analogs of NMDA receptor antagonists was prepared. Affinity for the NMDA receptor was determined by binding assays using the specific radioligand [3H] (2SR,4RS)-4-(phosphonomethyl)piperidine-2-carboxylic acid (CG...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/0968-0896(95)00087-w
更新日期：1995-09-01 00:00:00
abstract：:Pyrazolopyrimidines are the fused heterocyclic ring systems which structurally resemble purines which prompted biological investigations to assess their potential therapeutic significance. They are known to play a crucial role in numerous disease conditions. The advent of their first bioactivity as adenosine antagonis...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章,评审
doi：10.1016/j.bmc.2013.07.027
更新日期：2013-09-15 00:00:00
abstract：:The synthesis and structure-activity relationship of a new class of indole derivatives with low-nanomolar affinity for the SERT and high selectivity versus the 5-HT1A receptor were recently reported. Based on their chemical structure, four new indolylpropylamine derivatives which contain atoms to afford future labelin...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2008.05.006
更新日期：2008-06-15 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
pub_type： 杂志文章
doi：10.1016/j.bmc.2017.02.045
更新日期：2017-04-01 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
pub_type： 杂志文章
doi：10.1016/j.bmc.2018.02.026
更新日期：2018-05-01 00:00:00
abstract：:A novel peptidyl chemosensor (PySO2-His-Gly-Gly-Lys(PySO2)-NH2, 1) was synthesized by incorporation of two pyrene (Py) fluorophores into the tetrapeptide using sulfonamide group. Compound 1 exhibited selective fluorescence response towards Hg(II) over the other metal ions in aqueous buffered solutions. Furthermore, 1 ...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2013.09.058
更新日期：2013-12-15 00:00:00
abstract：:Leukemia stem cells (LSCs) account for the development of drug resistance and increased recurrence rate in acute myeloid leukemia (AML) patients. Targeted drug delivery to leukemia stem cells remains a major challenge in AML chemotherapy. Overexpressed interleukin-3 receptor alpha chain, CD123, on the surface of leuke...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2016.09.043
更新日期：2016-11-15 00:00:00
abstract：:A tetracyclic, conformationally constrained analogue of delta8-THC (2) has been synthesized in which a two carbon bridge exists between C2 and C2'. Two conceptually related syntheses of 2 are described, both of which employ 5,7-dimethoxy-4-oxo-1,2,3,4-tetrahydronaphthoic acid (11) as starting material. This substrate ...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/s0968-0896(98)80008-4
更新日期：1998-12-01 00:00:00
abstract：:An unusual class of diterpenoid natural products, 'cycloterpenals' (with a central cyclohexadienal core), that arise in nature by condensation of retinoids and other isoprenes, have been isolated from a variety of organisms including marine sponges as well as from the human eye. A milk whey protein has also demonstrat...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2008.07.030
更新日期：2008-08-15 00:00:00
abstract：:Recent years have seen a resurgence in drug discovery efforts aimed at the identification of covalent inhibitors which has led to an explosion of literature reports in this area and most importantly new approved therapies. These reports and breakthroughs highlight the significant investments made across the industry i...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2020.115865
更新日期：2021-01-01 00:00:00
abstract：:Photodynamic therapy (PDT) is a non-invasive, selective, and cost-effective cancer therapy. We previously reported that thiophene-based organic D-π-A sensitizers consist of an electron-donating (D) moiety, a π-conjugated bridge (π) moiety, and an electron-accepting (A) moiety, and are readily accessible and stable tem...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2020.115558
更新日期：2020-07-01 00:00:00
abstract：:We described the synthesis of a new congener series of 1,2,3-triazolyl-4-oxoquinolines and evaluated their ability to inhibit oseltamivir (OST)-resistant influenza strains. Oxoquinoline derivative 1i was the most potent compound within this series, inhibiting 94% of wild-type (WT) influenza neuraminidase (NA) activity...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2015.11.028
更新日期：2015-12-15 00:00:00
abstract：:An amine group was synthesized starting from an optically active bicyclo[2.2.1]heptane compound, which was then used to build the 5 atoms ring of a key 6-chloropurine intermediate. This was then reacted with ammonia and selected amines obtaining new adenine- and 6-substituted adenine conformationally constrained carbo...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2013.10.056
更新日期：2014-01-01 00:00:00
abstract：:A regioselective synthesis of 2,3-disubstituted tetrahydro-2H-indazols, mediated by alpha-zirconium sulfophenylphosphonate-methanephosphonate, was reported. Docking studies into the catalytic site of COX-2 were used to identify potential anti-inflammatory lead compounds. Two lead derivatives were chosen endowed with g...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2007.03.006
更新日期：2007-05-15 00:00:00
