Abstract:
:The discovery of new non-nucleoside antiviral compounds is of significant and growing interest for treating herpes virus infections due to the emergence of nucleoside-resistant strains. Using a whole cell virus-induced cytopathogenic assay, we tested a series of substituted triaryl heterocyclic compounds including acridones, xanthones, and acridines. The compounds which showed activity against Herpes Simplex-1 and/or Herpes Simplex-2 were further assayed for inhibition of topoisomerase activity to gain insight into the mechanism of action. The results indicate that the acridine analogs bearing substituted carboxamides and bulky 9-amino functionalities are able to inhibit herpes infections as well as inhibit topoisomerase II relaxation of supercoiled DNA. Given the mechanism of action of amsacrine (a closely related, well-studied 9-amino substituted acridine), the compounds were further tested in a DNA topoisomerase II cleavage assay to determine if the compounds function as poisons. The results show that the acridines synthesized in this study function through a different mechanism to that of amsacrine, most likely by blocking topoisomerase binding to DNA (akin to that of aclarubicin). This not only suggests a unique mechanism of action in treating herpes virus infections, but also may be of great interest in the development of anticancer agents that target topoisomerase II activity.
journal_name
Bioorg Med Chemjournal_title
Bioorganic & medicinal chemistryauthors
Goodell JR,Madhok AA,Hiasa H,Ferguson DMdoi
10.1016/j.bmc.2006.04.044subject
Has Abstractpub_date
2006-08-15 00:00:00pages
5467-80issue
16eissn
0968-0896issn
1464-3391pii
S0968-0896(06)00344-0journal_volume
14pub_type
杂志文章abstract::High-throughput screening of a small-molecule library identified a 5-triazolo-2-arylpyridazinone as a novel inhibitor of the important glycolytic enzyme 6-phosphofructo-2-kinase/2,6-bisphosphatase 3 (PFKFB3). Such inhibitors are of interest due to PFKFB3's control of the important glycolytic pathway used by cancer cel...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2013.12.041
更新日期:2014-02-01 00:00:00
abstract::Parkinson's disease (PD) is a common chronic degenerative disease of the central nervous system. Due to a rapidly aging society worldwide, PD morbidity is on the rise; however, the treatment of PD with conventional drugs carries serious adverse reactions and cannot fix the root cause of PD, the degeneration of dopamin...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章,评审
doi:10.1016/j.bmc.2016.02.030
更新日期:2016-04-01 00:00:00
abstract::2-Hydrazinyl-1,4,5,6-tetrahydropyrimidin-5-ol dihydrochloride 2, as well as 2-hydrazinyl-4,5-dihydro-1H-imidazole dihydrochloride 1, was synthesized as metal-free DNA cleaving agent. Agarose gel electrophoresis was used to assess the plasmid pUC 19 DNA cleavage activities in the presence of 1 and 2. DNA cleavage effic...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2009.05.044
更新日期:2009-07-01 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 ring-constrained phenylpropyloxyethylamines, partial opioid structure analogs and derivatives of a previously studied sigma (σ) receptor ligand, was synthesized and evaluated at σ and opioid receptors for receptor selectivity. The results of this study identified several compounds with nanomolar affinity a...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2013.06.068
更新日期:2013-09-01 00:00:00
abstract::Synthesis of a range of indomethacin analogues, required for investigation in combination toxicity assays, bearing both N-benzyl and N-benzoyl groups, is described. ...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/s0968-0896(00)00292-3
更新日期:2001-03-01 00:00:00
abstract::The PU-H58-dimers 13a-15b were efficiently synthesized and their biological properties were evaluated. The copper-catalyzed alkyne azide coupling was effective in simultaneously linking three components via a triazole formation to afford the target dimers. These synthesized dimers exhibited binding affinity to the N-t...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2010.05.075
更新日期:2010-08-01 00:00:00
abstract::Ethyl 3-aryl-3-oxopropanoates (aryl: phenyl, 2-fluorophenyl, 3-nitrophenyl, and 4-nitrophenyl) were reduced enantioselectively to the corresponding (S)-alcohols by the fungus Rhizopus arrhizus and other Rhizopus sp. The best results were generally obtained with Rhizopus arrhizus (wild type) and Rhizopus nivius NCIM 95...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2006.03.025
更新日期:2006-07-15 00:00:00
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::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::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
pub_type: 杂志文章
doi:10.1016/j.bmc.2016.12.021
更新日期:2017-02-01 00:00:00
abstract::Antibiotic resistance among clinically significant bacterial pathogens, such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant S. aureus (VRSA) is becoming a prevalent threat to public health, and new antibacterial agents with novel mechanisms of action hence are in an urgent need. As a pa...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2020.115729
更新日期:2020-11-01 00:00:00
abstract::To identify chemically and metabolically stable subtype-selective EP4 agonists, design and synthesis of a series of modified γ-lactam prostanoids has been continued. Prostanoids bearing 2-oxo-1,3-oxazolidine, 2-oxo-1,3-thiazolidine and 5-thioxopyrrolidine as a surrogate for the γ-hydroxycyclopentanone without a troubl...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2011.12.009
更新日期:2012-01-15 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
pub_type: 杂志文章
doi:10.1016/j.bmc.2016.10.028
更新日期:2017-01-01 00:00:00
abstract::A structure-activity relationship study was performed with ten 8-aminoquinoline-squaramides compounds active against liver stage malaria parasites, using human hepatoma cells (Huh7) infected by Plasmodium berghei parasites. In addition, their blood-schizontocidal activity was assessed against chloroquine-resistant W2 ...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2016.03.005
更新日期:2016-04-15 00:00:00
abstract::Because the activation of matrix metalloproteinases (MMP) is a key factor in the metastatic process, compounds with the ability to inhibit MMP activity have a potential in the treatment of tumor. From the examination of 2000 plant extracts, obovatal isolated from the extract of the leaves of Magnolia obovata THUNB was...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2007.03.081
更新日期:2007-06-15 00:00:00
abstract::A fluorescent cyclodextrin-Tb(III) complex is successfully synthesized and can include bile salts in its hydrophobic cavities. Therefore, it can efficiently induce the secondary assembly of small bile salt primary micelles to large micelle aggregates, and the aggregation process can be easily observed by transmission ...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2006.06.002
更新日期:2006-10-01 00:00:00
abstract::A class of 5-trifluoroacetylamino-1,3-dioxacycloalkanes, 5-benzoylamino-1,3-dioxacycloalkanes, and 5-amino-1,3-dioxacycloalkane compounds were stereoselectively synthesized as potential anti-inflammatory drug candidates. The anti-inflammatory activities of these compounds were tested using the xylene-induced mouse ear...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2005.09.068
更新日期:2006-03-01 00:00:00
abstract::The nitronate and nitrovinyl methods to synthesize indole glucosinolates (GLs) have been investigated. The results were applied to generally the most prevalent natural indole glucosinolates to synthesize 4-methoxyglucobrassicin (MGB) and neo-glucobrassicin (NGB) in moderate overall yield for the first time. The anti-i...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2013.12.003
更新日期:2014-01-15 00:00:00
abstract::In our previous study on discovering novel types of CCR3 antagonists, we found a fluoronaphthalene derivative (1) that exhibited potent CCR3 inhibitory activity with an IC(50) value of 20 nM. However, compound 1 also inhibited human cytochrome P450 2D6 (CYP2D6) with an IC(50) value of 400 nM. In order to reduce its CY...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2008.08.006
更新日期:2008-09-15 00:00:00
abstract::(R)-1-(10,11-Dihydro-dibenzo[b,f]azepin-5-yl)-3-methylamino-propan-2-ol ((R)-OHDMI) and (S,S)-1-cyclopentyl-2-(5-fluoro-2-methoxy-phenyl)-1-morpholin-2-yl-ethanol (CFMME) were synthesized and found to be potent inhibitors of norepinephrine reuptake. Each was labelled efficiently in its methyl group with carbon-11 (t(1...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2006.10.065
更新日期:2007-01-15 00:00:00
abstract::The chemical cross-linking of complexes of proteins with nucleic acids is often used in structural and mechanistic studies of these oftentimes unstable and transient complexes. To date, no method has been reported for the thiol-based conjugation of proteins with an RNA backbone, mainly because of instability of the mo...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2020.115741
更新日期:2020-12-01 00:00:00
abstract::5-HT(3A) receptor antagonists have been used mainly for the treatment of nausea and vomiting. These days, the antagonists are of special interest due to their therapeutic potential to treat other diseases such as depression, psychotic disorder, drug abuse, and irritable bowel syndrome. To discover novel 5-HT(3A) recep...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2009.04.029
更新日期:2009-07-01 00:00:00
abstract::This study aimed to investigate the relationships between structures of gene carrier molecules and their activities for gene delivery into cells. We compared 2 types of poly(L-lysine) as carriers, that is, dendritic poly(L-lysine) (KG6) and linear poly(L-lysine) (PLL). KG6 formed a neutral DNA complex, and its DNA com...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2006.09.033
更新日期:2007-01-01 00:00:00
abstract::The dopamine D4 receptor has been shown to play key roles in certain CNS pathologies including addiction to cigarette smoking. Thus, selective D4 ligands may be useful in treating some of these conditions. Previous studies in our laboratory have indicated that the piperazine analog of haloperidol exhibits selective an...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2014.04.026
更新日期:2014-06-15 00:00:00
abstract::The following study describes the synthesis of new benzanilide derivatives and their pharmacological investigation on smooth muscle preparations of guinea pigs. All compounds were synthesized in good yields and showed a spasmolytic activity without significant effect on vascular smooth muscles and heart muscle prepara...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2008.04.057
更新日期:2008-06-01 00:00:00
abstract::Two hybrid analogues of the kainic acid receptor agonists, 2-amino-3-(5-tert-butyl-3-hydroxy-4-isoxazolyl)propionic acid (ATPA) and (2S,4R)-4-methylglutamic acid ((2S,4R)-4-Me-Glu), were designed, synthesized, and characterized in radioligand binding assays using cloned ionotropic and metabotropic glutamic acid recept...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/s0968-0896(00)00304-7
更新日期:2001-04-01 00:00:00
abstract::A series of new N-substituted aminohydroxypyridines have been synthesized, pharmacologically evaluated and compared with their N-substituted oxazolopyridone analogs. The compound with the maximal combination of safety and analgesic efficacy was 3-[2-[4-(4-fluorophenyl)-1-piperazinyl]ethyl]amino-2-hydroxypyridine (comp...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/0968-0896(95)00080-z
更新日期:1995-07-01 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
pub_type: 杂志文章
doi:10.1016/j.bmc.2018.05.047
更新日期:2018-08-07 00:00:00
abstract::To develop agents for radionuclide imaging Aβ plaques in vivo, we prepared three fluorine-substituted analogs of arylbenzothiazole class; compound 2 has a high affinity for Aβ (K(i)=5.5nM) and the specific binding to Aβ in fluorescent staining. In preparation for the synthesis of these arylbenzothiazole analogs in rad...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2011.03.029
更新日期:2011-05-01 00:00:00