In the search for 1-[(2-hydroxyethoxy)-methyl]-6-(phenylthio)thymine (HEPT) derivatives, we have found several 5-ethyl-6-(phenylthio)uracil analogues to be highly potent and selective inhibitors of human immunodeficiency virus (HIV) type 1. 1-Benzyloxymethyl-5-ethyl-6-phenylthiouracil, most congener series, inhibits HIV-1 replication in a variety cell systems, including peripheral blood lymphocytes, at concentration 1.5-7.0 nM, which is lower by factor 10(3) than 50% antivirally effective...

5-Ethynyl-1-beta-D-ribofuranosylimidazole-4-carboxamide (EICAR) and 6'-(R)-6'-C-methylneplanocin A (TJ13025) are two novel antiviral agents which targeted against IMP dehydrogenase S-adenosylhomocysteine hydrolase, respectively. These compounds have been examined for their activities various strains of orthomyxoviruses (influenza virus) paramyxoviruses (parainfluenza virus, mumps measles respiratory syncytial in vitro. EICAR was 10- to 59-fold more active than ribavirin TJ13025 32- 330-fold...

By using an assay system based on a human hepatoblastoma cell line (HB611) that continuously synthesizes hepatitis B virus DNA, the following compounds were found to inhibit DNA synthesis at concentrations significantly lower than their minimum cytotoxic concentrations: 9-(2-phosphonylmethoxyethyl)-2,6-diaminopurine (PMEDAP), (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine, 9-(phosphonylmethoxyethyl)adenine, 2',3'-dideoxy-2',3'-didehydrocytidine, and 2',3'-dideoxycytidine. The most potent...

The inhibitory effects of 20 selected antiviral compounds on the replication adenoviruses (types 1 to 8) in vitro were investigated. While 18 ineffective, 2 compounds, namely (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine [(S)-HPMPA] and 9-[(2-hydroxy-1,3,2-dioxaphosphorinan-5-yl)oxymethyl]guanine P-oxide (2'-nor-cyclic GMP), highly effective against all adenovirus types assayed human embryonic fibroblast cultures. Their 50% doses 1.1 microgram/ml for (S)-HPMPA 4.1 micrograms/ml...

We investigated the effects of piceatannol on osteogenic differentiation human periodontal ligament fibroblasts (HPLFs). Treatment with increased alkaline phosphatase activity and gene molecules (Osteocalcin Runx2), but this was attenuated by mitogen-activated protein kinase (MAPK) inhibitors (PD098059 or SB203580). Our data suggest that promotes HPLFs activating MAPKs.

In the search for novel derivatives of 1-[2-(hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT), we have found that several 5-ethyl-6-(3,5-dimethylphenylthio)uracil and 5-ethyl-6-(3,5-dimethylbenzyl)uracil analogues are exquisitely potent selective inhibitors human immunodeficiency virus type 1 (HIV-1) replication in a variety cell culture systems. Of this series, 5-ethyl-1-ethoxymethyl-6-(3,5-dimethylbenzyl)uracil (E-EBU-dM) emerged as most active congener. Its 50% inhibitory concentration...

Passion fruit seed extract (PFSE), a product rich in stilbenes such as piceatannol and scirpusin B, has various physiological effects. It is unclear whether PFSE its stilbene derivatives inhibit cancer cell proliferation via human glyoxalase I (GLO I), the rate-limiting enzyme for detoxification of methylglyoxal. We examined anticancer effects two types lines with different GLO expression levels, NCI–H522 cells (highly-expressed I) HCT116 (lowly-expressed I). inhibited activity. In addition,...

Polyoxometalates have been shown to inhibit the replication of retro-, toga-, paramyxo- and herpesviruses. The primary mechanism anti-human immunodeficiency virus type 1 (HIV-1) action polyoxometalates seems be inhibition binding cells syncytium formation. Since myxoviruses HIV-1 are known interact with cytoplasmic membrane by adsorption penetration fusion infected uninfected cells, 25 were examined for anti-ortho-, anti-paramyxovirus anti-HIV-1 activity in vitro. Of compounds evaluated, 24...

Alzheimer's disease (AD) is a progressive neurodegenerative with accompanying perceptive disorder. We previously reported that decreasing levels of brain-derived neurotrophic factor (BDNF) promoted beta-amyloid (Aβ)-induced neuronal cell death in neuron-like differentiated SH-SY5Y (ndSH-SY5Y) human neuroblastoma cells an AD mimic model. investigated the neuroprotective effects passion fruit seed extract (PFSE) and one main stilbene compounds, piceatannol, model using ndSH-SY5Y cells. Both...

To investigate the mechanism of action 1-beta-D-arabinofuranosyl-(E)-5-(2-bromovinyl)uracil (BV-araU) on varicella zoster virus (VZV) replication, we examined metabolism drug in VZV-infected cells using 14C-labeled BV-araU. [14C]BV-araU was taken up by infected with thymidine kinase-positive (TK+)VZV, but not so much TK- or mock cells. Most radioactivity TK+ that were incubated recovered from their acid-soluble fraction, and little acid-insoluble fraction. By high performance liquid...

Twenty 2-thiopyrimidine nucleoside analogues were synthesized and examined for inhibitory activity against herpes simplex virus (HSV) type 1 2, varicella-zoster (VZV), human cytomegalovirus (HCMV) thymidine kinase-deficient HSV (HSV-TK-) replication in vitro. 2-thiouracil (thymine) arabinoside, 2'-deoxy-2-thiouridine (or 2-thiothymidine) their 5-halogenated derivatives showed anti-HSV both RPM18226 (human B-lymphoblastoid cells) MRC-5 embryo lung cells)....

Sixty polyoxometalates were examined for anti-influenza A virus (FluV-A) activity in vitro. Two of the most potent and least cytotoxic compounds, PM-504 K 9 H 5 (Ge 2 Ti 6 W 18 O 77 )16H O] PM-523 (iPrNH 3 ) [PTi2W 10 38 (O )9H ] selected further studies. Examination antiviral effects against other human ortho- paramyxoviruses revealed that both compounds had broad spectrum antimyxovirus activities. From a time addition study FACS analysis influenza infected cells, found not to inhibit...

Twenty 5-alkyl-2-thiopyrimidine nucleosides were newly synthesized and examined for antiviral activities against herpes simplex virus (HSV), varicella-zoster (VZV) human cytomegalovirus (HCMV). In this study, 2′-deoxy-5- alkyl-2-thiocytidine analogues had lower 50% effective concentration (EC50) values HSV- 1, 2/-deoxy-5-alkyl-2-thiouridine showed EC 50 VZV than their congeners of arabinoside form. Among the compounds examined, 2′-deoxy-5-ethyl 5-propyl- 2-thiocytidine (TN-53 TN-54) most...

Mizoribine (4-carbamoyl-1-β-D-ribofuranosylimidazo-lelium-5-olate), EICAR (5-ethynyl-1-β-D-ribofuranosylimi-dazole-4-carboxamide), mycophenolic acid and ribavirin are antiviral agents targeted for inosine monophosphate (IMP) dehydrogenase. These compounds have been examined their activities against orthomyxoviruses [influenza viruses (FluV)] paramyxoviruses [parainfluenza (PFIuV), mumps virus, measles virus (MLSV) respiratory syncytial (RSV)] in vitro. was 1- to 9-fold more active than RSV,...

The ribavirin concentration in hamster brains was measured by a high-performance liquid chromatography (HPLC) system and bioassay system. When administered intracranially at dosage of 10 mg/kg body weight per day for days, which results 100% survival hamsters infected with subacute sclerosing panencephalitis (SSPE) virus inhibits the replication SSPE brains, estimated HPLC kept higher than 50 micrograms/g days. effective vivo corresponds to completely vitro. maximal tolerable calculated be...

Piceatannol (PIC), a phytochemical, is abundant in passion fruit (Passiflora edulis) seeds. In this study, we investigated the effects of PIC on expression levels antioxidant enzymes C2C12 skeletal muscle cells and compared its with those analogues polyphenols. We also evaluated hydrogen peroxide-induced accumulation reactive oxygen species myotubes. Treatment led to dose-dependent upregulation heme oxygenase-1 (Ho-1) superoxide dismutase 1 (Sod1) mRNA was most potent inducer Ho-1 among...

Among thirteen newly synthesized pyridobenzoazole derivatives which have been examined for anti-myxovirus and antiherpesvirus activities, three benzimidazoles emerged as potent anti-orthomyxo- or paramyxovirus compounds. 4-Cyano-2-benzamide-1-oxo-1,5-dihydropyrido[1,2a]benzimidazole (CBO-PB) showed broad antiviral activities against paramyxo-and orthomyxoviruses with EC 50 of 0.1–2.0 μg ml −1 , 2-cyano-1-amino CBO-PB (CCI-PB) were inhibitory to paramyxoviruses at 1.4–8.5 (μg by a plaque...

CD14 is a pattern recognition receptor on myeloid cells and plays pivotal role in an innate immune system that responsible for Gram-negative Gram-positive bacteria infection. Lipopolysaccharide (LPS), cell wall component of bacteria, can induce production large quantity proinflammatory cytokines into the circulation mediated by CD14-mediated macrophages monocytes. These eventually cause septic shock. Several vitro vivo studies have shown suppression function antibody led to inhibition such...

A varicella-zoster virus (VZV) strain resistant to 5-iodo-2'-deoxyuridine (IdUrd) and 5-bromo-2'-deoxyuridine (BrdUrd) but sensitive (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVdUrd) (E)-5-(2-iodovinyl)-2'-deoxyuridine (IVdUrd) was isolated. The 2'-deoxythymidine (dThd) kinase of this mutant (Ito) characterized; it much less efficient in phosphorylating dThd, 2'-deoxycytidine, BrdUrd than were the dThd kinases from wild-type (CaQu, Kobayashi) VZV strains. Ito had a markedly decreased affinity...

A natural sulphated mucopolysaccharide (OKU40), extracted from a marine plant Dinoflagellata, and an artificial polysaccharide (OKU41), prepared Pseudomonas, displayed antiviral activities against several enveloped viruses. OKU40 OKU41 were found to be homogenous in electrophoresis sedimation velocity had molecular weight of 8.0 × 10 6 5.0 5 respectively. The sulphation rate was 8.9% 5.4%, Each inhibited the cytopathic effect human immunodeficiency virus type 1 (HIV-1), 2 (HIV-2)...

The neurofibromatosis type 1 (NF1) gene encodes a protein, neurofibromin, containing GTPase-activating protein-related domain (GRD) that stimulates intrinsic GTPase activity of Ras protein. By screening randomly mutagenized NF1-GRD library in Saccharomyces cerevisiae, we isolated two mutants (NF201 and NF204) with single amino acid substitutions, which suppress the heat shock-sensitive phenotype RAS2(G19V) mutant. also oncogenic Ras-induced transformation NIH 3T3 mouse fibroblasts (Nakafuku,...