The effect of substitution on the pyrimidine moiety of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) and 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)-2-thiothymine (HEPT-S) on anti-HIV-1 activity was investigated by synthesizing a series of 5-methyl-6-(arylthio) and 5-substituted-6-(phenylthio) derivatives. Preparation of the 5-methyl-6-(arylthio) derivatives was carried out based on either LDA lithiation of 1-[[2-(tert-butyldimethylsiloxy)ethoxy]methyl]thymine (3) and 1-[[2-(tert-butyldimethylsiloxy)ethoxy]methyl]-2-thiothymine (4) followed by reaction with diaryl disulfides or an addition-elimination reaction of 1-[[2-(tert-butyldimethylsiloxy)ethoxy]-methyl]-6- (phenylsulfinyl)thymine (31) with aromatic thiols. Preparation of the 5-substituted-6-(phenylthio) derivatives was carried out based on either C-5 lithiation of the 1-[[2-(tert-butyldimethylsiloxy)ethoxy]methyl]-6-(phenylthio)uraci l (41) with LTMP or the LDA lithiation of 5-alkyl-1-[[2-(tert-butyldimethylsiloxy)ethoxy]methyl]-2-thiouraci l derivatives 45-47. Substitution at the meta position of the C-6-(phenylthio) ring by the methyl group improved the original anti-HIV-1 activity of HEPT, and introduction of two m-methyl groups to the phenylthio ring further potentiated the activity [EC50: 6-[(3,5-dimethylphenyl)thio]-1-[(2-hydroxyethoxy)methyl]thymine (28), 0.26 microM; 6-[(3,5-dimethylphenyl)thio]-1-[(2-hydroxyethoxy)methyl]-2-thiothymin e (30), 0.22 microM]. When the 5-methyl group was replaced by an ethyl or an isopropyl group, the anti-HIV-1 activity of HEPT was also improved remarkably [EC50: 5-ethyl-1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)-2-thiouracil (48), 0.11 microM; 5-isopropyl-1-[(2-hydroxyethoxy)-methyl]-6-(phenylthio)-2-thiouracil (50), 0.059 microM; 5-ethyl-1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)-2-thiouracil (54), 0.12 microM; 5-isopropyl-1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)-2-thiouracil (56), 0.063 microM]. 6-[(3,5-Dimethylphenyl)thio]-5-ethyl-1-[(2-hydroxyethoxy)methyl]thymine derivatives 51 and 57 and 6-[(3,5-dimethylphenyl)thio]-5-isopropyl-1-[(2- hydroxyethoxy)methyl]thymine derivatives 52 and 58 inhibited the replication of HIV-1 in the nanomolar concentration range.
Electron microscopy of erythrocytes of Atlantic cod, Gadus morhua, with piscine erythrocytic necrosis (PEN) shows a small cytoplasmic viroplasm (~ 1 μm), often with an adjacent coherent group of large (330 nm) icosahedral virions. The viroplasm is Feulgen-positive, so the agent is an erythrocyte icosahedral cytoplasmic deoxyribovirus (EICDV) analogous to others reported in red cells of poikilotherms. PEN lesions in cod blood cells were found in 11–16% of samples from New Brunswick, Maine, and Georges Bank. PEN was found in cod of 15–80 cm total length taken at depths of 5–90 m. Incidence in the Georges Bank area was higher at depths of about 55 m. Intensity of infection varied from < 0.01 to ~ 99% of mature red cells, without obvious relation to cod size, sex, or condition, or to depth at which taken. PEN infections are reported in various other fish species and in other areas. Key words: viral infections, cytology, ultrastructure, morphology, pathology, Atlantic coast fishes
. Dicauda atherinoidi n.g., n. sp. (Protozoa: Myxosporida) was found in feral minnows, Notropis atherinoides (Cyprinidae), from western Lake Erie (Sterling State Park), Michigan, and the lower Mohawk and Hudson Rivers, New York. Dicauda, closely related to Myxobolus, differs from it in having two, occasionally three or more, rigid tail‐like possibly mucoid appendages attached to the sutural ridge. The cysts are subdermal and most abundant on the head. Histological damage is not striking.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.