The Experts below are selected from a list of 114 Experts worldwide ranked by ideXlab platform
Thomas A. Krenitsky - One of the best experts on this subject based on the ideXlab platform.
-
Purine Arabinosides as Inhibitors of Human Haemopoietic Progenitor Cells
Antiviral Chemistry and Chemotherapy, 1992Co-Authors: Devron Averett, George W. Koszalka, Thomas Spector, H. N. Steinberg, Thomas A. KrenitskyAbstract:Four purine Arabinosides that inhibit varicella-zoster virus (VZV) replication in vitro were tested as inhibitors of colony formation by progenitor cells from normal human bone marrow. In general, erythroid burst forming cells (BFU-E) were more sensitive to inhibition by these compounds than were either erythroid colony forming cells (CFY-E) or granulocyte/macrophage colony formation (IC 50 ) was observed for BFU-E in the presence of 8 μm 6-methoxypurine Arabinoside. Adenine Arabinoside and hypoxanthine Arabinoside had IC 50 values of 1 μM and 4 μM respectively, whereas 6-ethyxypurine Arabinoside was not inhibitory (IC 50 >50 μM)
-
6-N-substituted derivatives of adenine Arabinoside as selective inhibitors of varicella-zoster virus.
Antimicrobial agents and chemotherapy, 1991Co-Authors: George W. Koszalka, Devron Averett, James A. Fyfe, G B Roberts, Thomas Spector, Karen K. Biron, Thomas A. KrenitskyAbstract:A series of 6-alkylaminopurine Arabinosides were synthesized and found to inhibit varicella-zoster virus (VZV). The antiviral activities of these nucleosides were limited to VZV. None of the other viruses tested in the herpesvirus family were affected. The in vitro antiviral potencies of the 18 Arabinosides correlated with their efficiencies as substrates of the VZV-encoded thymidine kinase in all but one case. The Arabinosides of 6-methylaminopurine and 6-dimethylaminopurine were the most potent analogs, with 50% inhibitory concentrations against VZV of 3 and 1 microM, respectively. They were not cytotoxic to uninfected MRC-5 cells, human Detroit 98 cells, or mouse L cells (50% inhibitory concentration, greater than 100 microM). Neither 6-methylaminopurine Arabinoside nor 6-dimethylaminopurine Arabinoside was detectably phosphorylated by either adenosine kinase or 29-deoxycytidine kinase. These two alkylaminopurine Arabinosides were also resistant to deamination catalyzed by adenosine deaminase. The VZV-dependent phosphorylation of these nucleosides offers the possibility of a potent and highly selective therapy for VZV infection.
-
6-Methoxypurine Arabinoside as a selective and potent inhibitor of varicella-zoster virus.
Antimicrobial agents and chemotherapy, 1991Co-Authors: Devron Averett, George W. Koszalka, James A. Fyfe, G B Roberts, D. J. M. Purifoy, Thomas A. KrenitskyAbstract:Seven 6-alkoxypurine Arabinosides were synthesized and evaluated for in vitro activity against varicella-zoster virus (VZV). The simplest of the series, 6-methoxypurine Arabinoside (ara-M), was the most potent, with 50% inhibitory concentrations ranging from 0.5 to 3 microM against eight strains of VZV. This activity was selective. The ability of ara-M to inhibit the growth of a variety of human cell lines was at least 30-fold less (50% effective concentration, greater than 100 microM) than its ability to inhibit the virus. Enzyme studies suggested the molecular basis for these results. Of the seven 6-alkoxypurine Arabinosides, ara-M was the most efficient substrate for VZV-encoded thymidine kinase as well as the most potent antiviral agent. In contrast, it was not detectably phosphorylated by any of the three major mammalian nucleoside kinases. Upon direct comparison, ara-M was appreciably more potent against VZV than either acyclovir or adenine Arabinoside (ara-A). However, in the presence of an adenosine deaminase inhibitor, the Arabinosides of adenine and 6-methoxypurine were equipotent but not equally selective; the adenine congener had a much less favorable in vitro chemotherapeutic index. Again, this result correlated with data from enzyme studies in that ara-A, unlike ara-M, was a substrate for two mammalian nucleoside kinases. Unlike acyclovir and ara-A, ara-M had no appreciable activity against other viruses of the herpes group. The potency and selectivity of ara-M as an anti-VZV agent in vitro justify its further study.
Akiyo Sakushima - One of the best experts on this subject based on the ideXlab platform.
-
structural studies of zoospore attractants from trachelospermum jasminoides var pubescens taxifolin 3 o glycosides
Phytochemical Analysis, 2006Co-Authors: Shinzo Hosoi, Eri Shimizu, Kosei Ohno, Ryozo Yokosawa, Shiro Kuninaga, Maksut Coskun, Akiyo SakushimaAbstract:(2S, 3S)-Taxifolin 3-O-Arabinoside, a new dihydroflavonol glycoside, together with the known substances, (2R 3R)-taxifolin 3-O-Arabinoside, astragalin, isoquercitrin, and cosmosiin, were isolated from the leaves of Trachelospermum jasminoides var. pubescens. Structural elucidation was carried out by spectroscopic methods, and the absolute configurations of C-2 and C-3 in taxifolin 3-O-Arabinosides were determined on the basis of circular dichroism. Unlike the dihydroflavonol glycosides, (2R 3R)-taxifolin 3-O-glucoside and (2R, 3R-taxifolin 3-O-Arabinoside, the novel (2S, 3S)-taxifolin 3-O-Arabinoside is not effective as a zoospore attractant of the plant pathogenic fungus Aphanomyces cochlioides.
George W. Koszalka - One of the best experts on this subject based on the ideXlab platform.
-
Purine Arabinosides as Inhibitors of Human Haemopoietic Progenitor Cells
Antiviral Chemistry and Chemotherapy, 1992Co-Authors: Devron Averett, George W. Koszalka, Thomas Spector, H. N. Steinberg, Thomas A. KrenitskyAbstract:Four purine Arabinosides that inhibit varicella-zoster virus (VZV) replication in vitro were tested as inhibitors of colony formation by progenitor cells from normal human bone marrow. In general, erythroid burst forming cells (BFU-E) were more sensitive to inhibition by these compounds than were either erythroid colony forming cells (CFY-E) or granulocyte/macrophage colony formation (IC 50 ) was observed for BFU-E in the presence of 8 μm 6-methoxypurine Arabinoside. Adenine Arabinoside and hypoxanthine Arabinoside had IC 50 values of 1 μM and 4 μM respectively, whereas 6-ethyxypurine Arabinoside was not inhibitory (IC 50 >50 μM)
-
6-N-substituted derivatives of adenine Arabinoside as selective inhibitors of varicella-zoster virus.
Antimicrobial agents and chemotherapy, 1991Co-Authors: George W. Koszalka, Devron Averett, James A. Fyfe, G B Roberts, Thomas Spector, Karen K. Biron, Thomas A. KrenitskyAbstract:A series of 6-alkylaminopurine Arabinosides were synthesized and found to inhibit varicella-zoster virus (VZV). The antiviral activities of these nucleosides were limited to VZV. None of the other viruses tested in the herpesvirus family were affected. The in vitro antiviral potencies of the 18 Arabinosides correlated with their efficiencies as substrates of the VZV-encoded thymidine kinase in all but one case. The Arabinosides of 6-methylaminopurine and 6-dimethylaminopurine were the most potent analogs, with 50% inhibitory concentrations against VZV of 3 and 1 microM, respectively. They were not cytotoxic to uninfected MRC-5 cells, human Detroit 98 cells, or mouse L cells (50% inhibitory concentration, greater than 100 microM). Neither 6-methylaminopurine Arabinoside nor 6-dimethylaminopurine Arabinoside was detectably phosphorylated by either adenosine kinase or 29-deoxycytidine kinase. These two alkylaminopurine Arabinosides were also resistant to deamination catalyzed by adenosine deaminase. The VZV-dependent phosphorylation of these nucleosides offers the possibility of a potent and highly selective therapy for VZV infection.
-
6-Methoxypurine Arabinoside as a selective and potent inhibitor of varicella-zoster virus.
Antimicrobial agents and chemotherapy, 1991Co-Authors: Devron Averett, George W. Koszalka, James A. Fyfe, G B Roberts, D. J. M. Purifoy, Thomas A. KrenitskyAbstract:Seven 6-alkoxypurine Arabinosides were synthesized and evaluated for in vitro activity against varicella-zoster virus (VZV). The simplest of the series, 6-methoxypurine Arabinoside (ara-M), was the most potent, with 50% inhibitory concentrations ranging from 0.5 to 3 microM against eight strains of VZV. This activity was selective. The ability of ara-M to inhibit the growth of a variety of human cell lines was at least 30-fold less (50% effective concentration, greater than 100 microM) than its ability to inhibit the virus. Enzyme studies suggested the molecular basis for these results. Of the seven 6-alkoxypurine Arabinosides, ara-M was the most efficient substrate for VZV-encoded thymidine kinase as well as the most potent antiviral agent. In contrast, it was not detectably phosphorylated by any of the three major mammalian nucleoside kinases. Upon direct comparison, ara-M was appreciably more potent against VZV than either acyclovir or adenine Arabinoside (ara-A). However, in the presence of an adenosine deaminase inhibitor, the Arabinosides of adenine and 6-methoxypurine were equipotent but not equally selective; the adenine congener had a much less favorable in vitro chemotherapeutic index. Again, this result correlated with data from enzyme studies in that ara-A, unlike ara-M, was a substrate for two mammalian nucleoside kinases. Unlike acyclovir and ara-A, ara-M had no appreciable activity against other viruses of the herpes group. The potency and selectivity of ara-M as an anti-VZV agent in vitro justify its further study.
Devron Averett - One of the best experts on this subject based on the ideXlab platform.
-
Purine Arabinosides as Inhibitors of Human Haemopoietic Progenitor Cells
Antiviral Chemistry and Chemotherapy, 1992Co-Authors: Devron Averett, George W. Koszalka, Thomas Spector, H. N. Steinberg, Thomas A. KrenitskyAbstract:Four purine Arabinosides that inhibit varicella-zoster virus (VZV) replication in vitro were tested as inhibitors of colony formation by progenitor cells from normal human bone marrow. In general, erythroid burst forming cells (BFU-E) were more sensitive to inhibition by these compounds than were either erythroid colony forming cells (CFY-E) or granulocyte/macrophage colony formation (IC 50 ) was observed for BFU-E in the presence of 8 μm 6-methoxypurine Arabinoside. Adenine Arabinoside and hypoxanthine Arabinoside had IC 50 values of 1 μM and 4 μM respectively, whereas 6-ethyxypurine Arabinoside was not inhibitory (IC 50 >50 μM)
-
6-N-substituted derivatives of adenine Arabinoside as selective inhibitors of varicella-zoster virus.
Antimicrobial agents and chemotherapy, 1991Co-Authors: George W. Koszalka, Devron Averett, James A. Fyfe, G B Roberts, Thomas Spector, Karen K. Biron, Thomas A. KrenitskyAbstract:A series of 6-alkylaminopurine Arabinosides were synthesized and found to inhibit varicella-zoster virus (VZV). The antiviral activities of these nucleosides were limited to VZV. None of the other viruses tested in the herpesvirus family were affected. The in vitro antiviral potencies of the 18 Arabinosides correlated with their efficiencies as substrates of the VZV-encoded thymidine kinase in all but one case. The Arabinosides of 6-methylaminopurine and 6-dimethylaminopurine were the most potent analogs, with 50% inhibitory concentrations against VZV of 3 and 1 microM, respectively. They were not cytotoxic to uninfected MRC-5 cells, human Detroit 98 cells, or mouse L cells (50% inhibitory concentration, greater than 100 microM). Neither 6-methylaminopurine Arabinoside nor 6-dimethylaminopurine Arabinoside was detectably phosphorylated by either adenosine kinase or 29-deoxycytidine kinase. These two alkylaminopurine Arabinosides were also resistant to deamination catalyzed by adenosine deaminase. The VZV-dependent phosphorylation of these nucleosides offers the possibility of a potent and highly selective therapy for VZV infection.
-
6-Methoxypurine Arabinoside as a selective and potent inhibitor of varicella-zoster virus.
Antimicrobial agents and chemotherapy, 1991Co-Authors: Devron Averett, George W. Koszalka, James A. Fyfe, G B Roberts, D. J. M. Purifoy, Thomas A. KrenitskyAbstract:Seven 6-alkoxypurine Arabinosides were synthesized and evaluated for in vitro activity against varicella-zoster virus (VZV). The simplest of the series, 6-methoxypurine Arabinoside (ara-M), was the most potent, with 50% inhibitory concentrations ranging from 0.5 to 3 microM against eight strains of VZV. This activity was selective. The ability of ara-M to inhibit the growth of a variety of human cell lines was at least 30-fold less (50% effective concentration, greater than 100 microM) than its ability to inhibit the virus. Enzyme studies suggested the molecular basis for these results. Of the seven 6-alkoxypurine Arabinosides, ara-M was the most efficient substrate for VZV-encoded thymidine kinase as well as the most potent antiviral agent. In contrast, it was not detectably phosphorylated by any of the three major mammalian nucleoside kinases. Upon direct comparison, ara-M was appreciably more potent against VZV than either acyclovir or adenine Arabinoside (ara-A). However, in the presence of an adenosine deaminase inhibitor, the Arabinosides of adenine and 6-methoxypurine were equipotent but not equally selective; the adenine congener had a much less favorable in vitro chemotherapeutic index. Again, this result correlated with data from enzyme studies in that ara-A, unlike ara-M, was a substrate for two mammalian nucleoside kinases. Unlike acyclovir and ara-A, ara-M had no appreciable activity against other viruses of the herpes group. The potency and selectivity of ara-M as an anti-VZV agent in vitro justify its further study.
Shinzo Hosoi - One of the best experts on this subject based on the ideXlab platform.
-
structural studies of zoospore attractants from trachelospermum jasminoides var pubescens taxifolin 3 o glycosides
Phytochemical Analysis, 2006Co-Authors: Shinzo Hosoi, Eri Shimizu, Kosei Ohno, Ryozo Yokosawa, Shiro Kuninaga, Maksut Coskun, Akiyo SakushimaAbstract:(2S, 3S)-Taxifolin 3-O-Arabinoside, a new dihydroflavonol glycoside, together with the known substances, (2R 3R)-taxifolin 3-O-Arabinoside, astragalin, isoquercitrin, and cosmosiin, were isolated from the leaves of Trachelospermum jasminoides var. pubescens. Structural elucidation was carried out by spectroscopic methods, and the absolute configurations of C-2 and C-3 in taxifolin 3-O-Arabinosides were determined on the basis of circular dichroism. Unlike the dihydroflavonol glycosides, (2R 3R)-taxifolin 3-O-glucoside and (2R, 3R-taxifolin 3-O-Arabinoside, the novel (2S, 3S)-taxifolin 3-O-Arabinoside is not effective as a zoospore attractant of the plant pathogenic fungus Aphanomyces cochlioides.