The Experts below are selected from a list of 414 Experts worldwide ranked by ideXlab platform
Hiroshi Nagai - One of the best experts on this subject based on the ideXlab platform.
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neo Aplysiatoxin a isolated from okinawan cyanobacterium moorea producens
Molecules, 2020Co-Authors: Mioko Kawaguchi, Yueyun Xiao, Masayuki Fukuoka, Hajime Uchida, Masayuki Satake, Botao Zhang, Hiroshi NagaiAbstract:A new Aplysiatoxin derivative, neo-Aplysiatoxin A (1), along with seven known compounds, neo-debromoAplysiatoxin A (2), dolastatin 3 (3), lyngbic acid (4), malyngamide M (5), hermitamide A (6), (−)-loliolide (7), and (+)-epiloliolide (8), was isolated from the Okinawan cyanobacterium Moorea producens. Their structures were elucidated on the basis of spectroscopic data, including high-resolution mass spectrometry and nuclear magnetic resonance. The compounds were evaluated for cytotoxic and diatom growth inhibition activities.
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Oscillatoxin I: A New Aplysiatoxin Derivative, from a Marine Cyanobacterium.
Toxins, 2019Co-Authors: Hiroshi Nagai, Mioko Kawaguchi, Hajime Uchida, Kazutaka Hayashi, Shingo Sato, Kaori Iida, Masayuki SatakeAbstract:Cyanobacteria have been shown to produce a number of bioactive compounds, including toxins. Some bioactive compounds obtained from a marine cyanobacterium Moorea producens (formerly Lyngbya majuscula) have been recognized as drug leads; one of these compounds is Aplysiatoxin. We have isolated various Aplysiatoxin derivatives from a M. producens sample obtained from the Okinawan coastal area. The frozen sample was extracted with organic solvents. The ethyl acetate layer was obtained from the crude extracts via liquid-liquid partitioning, then separated by HPLC using a reversed-phase column. Finally, 1.1 mg of the compound was isolated. The chemical structure of the isolated compound was elucidated with spectroscopic methods, using HR-MS and 1D and 2D NMR techniques, and was revealed to be oscillatoxin I, a new member of the Aplysiatoxin family. Oscillatoxin I showed cytotoxicity against the L1210 mouse lymphoma cell line and diatom growth-inhibition activity against the marine diatom Nitzschia amabilis.
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new Aplysiatoxin derivatives from the okinawan cyanobacterium moorea producens
Tetrahedron, 2019Co-Authors: Hiroshi Nagai, Minami Watanabe, Mioko Kawaguchi, Yueyun Xiao, Hajime Uchida, Ryuichi Watanabe, Kazutaka Hayashi, Shingo Sato, Masayuki SatakeAbstract:Abstract The marine cyanobacterium Moorea producens is a rich source of diverse compounds that possess a variety of biological activities. In the present study, eight new Aplysiatoxin derivatives, namely 6, 8–13, and 15, along with Aplysiatoxin (1), debromoAplysiatoxin (2), 3-methoxyAplysiatoxin (3), anhydroAplysiatoxin (4), anhydrodebromoAplysiatoxin (5), oscillatoxin B2 (7), and 30-methyloscillatoxin D (14) were isolated and identified from the Okinawan M. producens. In cytotoxicity and diatom growth inhibition tests, the fifteen compounds tested (1–15) showed moderate or no activity at a concentration of 10 μg/mL.
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synthesis and structure activity studies of simplified analogues of Aplysiatoxin with antiproliferative activity like bryostatin 1
Pure and Applied Chemistry, 2012Co-Authors: Kazuhiro Irie, Harukuni Tokuda, Ryo C. Yanagita, Hiroaki Kamachi, Keisuke Tanaka, Akira Murakami, Nobutaka Suzuki, Masayuki Kikumori, Hiroshi NagaiAbstract:Protein kinase C (PKC) isozymes are promising targets for anticancer therapy. Bryostatin-1 (bryo-1), a unique PKC activator with little tumor-promoting activity, is cur- rently in clinical trials for the treatment of cancer. However, its limited availability from nat- ural sources and its synthetic complexity have hampered studies of its mode of action and structural optimization as a therapeutic agent. The development of synthetically more acces- sible compounds with bryo-1-like activities is thus needed. Recently, we developed a simple and less lipophilic analogue of tumor-promoting Aplysiatoxin (ATX) (aplog-1) as a promising lead for bryo-1-like anticancer drugs. Structure-activity studies suggested that local hydro - phobicity around the spiroketal moiety of aplog-1 is a crucial determinant of its antiprolifer- ative activity. The hydrophobic analogue (12,12-dimethyl-aplog-1) displayed more potent antiproliferative activity. Moreover, it showed little tumor-promoting activity and even sup- pressed the tumor promotion by 12-O-tetradecanoylphorbol 13-acetate (TPA) in vivo and in vitro. Aplog-1 and bryo-1 bound selectively to novel PKC isozymes (δ, η, and θ) while tumor promoters bound to both conventional and novel PKC isozymes. These results suggest that the unique biological activities of aplog-1 and bryo-1 are ascribable in part to the ability to bind to PKCδ, but weak binding to conventional PKC isozymes might also be important.
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Synthesis and structure–activity studies of simplified analogues of Aplysiatoxin with antiproliferative activity like bryostatin-1
Pure and Applied Chemistry, 2012Co-Authors: Kazuhiro Irie, Hiroshi Nagai, Harukuni Tokuda, Ryo C. Yanagita, Hiroaki Kamachi, Keisuke Tanaka, Akira Murakami, Nobutaka Suzuki, Masayuki Kikumori, Kiyotake SuenagaAbstract:Protein kinase C (PKC) isozymes are promising targets for anticancer therapy. Bryostatin-1 (bryo-1), a unique PKC activator with little tumor-promoting activity, is cur- rently in clinical trials for the treatment of cancer. However, its limited availability from nat- ural sources and its synthetic complexity have hampered studies of its mode of action and structural optimization as a therapeutic agent. The development of synthetically more acces- sible compounds with bryo-1-like activities is thus needed. Recently, we developed a simple and less lipophilic analogue of tumor-promoting Aplysiatoxin (ATX) (aplog-1) as a promising lead for bryo-1-like anticancer drugs. Structure-activity studies suggested that local hydro - phobicity around the spiroketal moiety of aplog-1 is a crucial determinant of its antiprolifer- ative activity. The hydrophobic analogue (12,12-dimethyl-aplog-1) displayed more potent antiproliferative activity. Moreover, it showed little tumor-promoting activity and even sup- pressed the tumor promotion by 12-O-tetradecanoylphorbol 13-acetate (TPA) in vivo and in vitro. Aplog-1 and bryo-1 bound selectively to novel PKC isozymes (δ, η, and θ) while tumor promoters bound to both conventional and novel PKC isozymes. These results suggest that the unique biological activities of aplog-1 and bryo-1 are ascribable in part to the ability to bind to PKCδ, but weak binding to conventional PKC isozymes might also be important.
Kazuhiro Irie - One of the best experts on this subject based on the ideXlab platform.
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Synthesis and biological activities of simplified Aplysiatoxin analogs focused on the CH/π interaction.
Bioorganic & medicinal chemistry letters, 2020Co-Authors: Takumi Kobayashi, Ryo C. Yanagita, Kazuhiro IrieAbstract:Abstract DebromoAplysiatoxin (DAT) is a potent protein kinase C (PKC) activator with tumor-promoting and pro-inflammatory activities. Irie and colleagues have found that 10-methyl-aplog-1 (1), a simplified analog of DAT, has strong anti-proliferative activity against several cancer cell lines with few adverse effects. Therefore, 1 is a potential lead compound for cancer therapy. We synthesized a new derivative 2 which has a naphthalene ring at the side chain terminal position instead of a benzene ring, to increase CH/π interactions with Pro-241 of the PKCδ-C1B domain. Based on the synthetic route of 1, 2 was convergently synthesized in 26 linear steps from 6-hydroxy-1-naphthoic acid with an overall yield of 0.18%. Although the anti-proliferative activity of 2 was more potent than that of 1, the binding potency of 2 to the PKCδ-C1B domain did not exceed that of 1. Molecular dynamics simulation indicated the capability of 2 to simultaneously form hydrogen bonds and CH/π interactions with the PKCδ-C1B domain. Focusing on the hydrogen bonds, their geometry in the binding modes involving the CH/π interactions seemed to be sub-optimal, which may explain the slightly lower affinity of 2 compared to 1. This study could be of help in optimizing such interactions and synthesizing a promising lead cancer compound.
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Binding mode prediction of Aplysiatoxin, a potent agonist of protein kinase C, through molecular simulation and structure-activity study on simplified analogs of the receptor-recognition domain.
Bioorganic & medicinal chemistry, 2016Co-Authors: Yoshiki Ashida, Ryo C. Yanagita, Chise Takahashi, Yasuhiro Kawanami, Kazuhiro IrieAbstract:Abstract Aplysiatoxin (ATX) is a naturally occurring tumor promoter isolated from a sea hare and cyanobacteria. ATX binds to, and activates, protein kinase C (PKC) isozymes and shows anti-proliferative activity against human cancer cell lines. Recently, ATX has attracted attention as a lead compound for the development of novel anticancer drugs. In order to predict the binding mode between ATX and protein kinase Cδ (PKCδ) C1B domain, we carried out molecular docking simulation, atomistic molecular dynamics simulation in phospholipid membrane environment, and structure–activity study on a simple acyclic analog of ATX. These studies provided the binding model where the carbonyl group at position 27, the hydroxyl group at position 30, and the phenolic hydroxyl group at position 20 of ATX were involved in intermolecular hydrogen bonding with the PKCδ C1B domain, which would be useful for the rational design of ATX derivatives as anticancer lead compounds.
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Synthesis and biological activities of the amide derivative of aplog-1, a simplified analog of Aplysiatoxin with anti-proliferative and cytotoxic activities.
Bioscience biotechnology and biochemistry, 2015Co-Authors: Yusuke Hanaki, Harukuni Tokuda, Ryo C. Yanagita, Takahiro Sugahara, Misako Aida, Nobutaka Suzuki, Kazuhiro IrieAbstract:Aplog-1 is a simplified analog of the tumor-promoting Aplysiatoxin with anti-proliferative and cytotoxic activities against several cancer cell lines. Our recent findings have suggested that protein kinase Cδ (PKCδ) could be one of the target proteins of aplog-1. In this study, we synthesized amide-aplog-1 (3), in which the C-1 ester group was replaced with an amide group, to improve chemical stability in vivo. Unfortunately, 3 exhibited seventy-fold weaker binding affinity to the C1B domain of PKCδ than that of aplog-1, and negligible anti-proliferative and cytotoxic activities even at 10−4 M. A conformational analysis and density functional theory calculations indicated that the stable conformation of 3 differed from that of aplog-1. Since 27-methyl and 27-methoxy derivatives (1, 2) without the ability to bind to PKC isozymes exhibited marked anti-proliferative and cytotoxic activities at 10−4 M, 3 may be an inactive control to identify the target proteins of aplogs.
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synthesis and biological activities of simplified analogs of the natural pkc ligands bryostatin 1 and Aplysiatoxin
Chemical Record, 2014Co-Authors: Kazuhiro Irie, Ryo C. YanagitaAbstract:: Protein kinase C (PKC) isozymes play central roles in signal transduction on the cell surface and could serve as promising therapeutic targets of intractable diseases like cancer, Alzheimer's disease, and acquired immunodeficiency syndrome (AIDS). Although natural PKC ligands like phorbol esters, ingenol esters, and teleocidins have the potential to become therapeutic leads, most of them are potent tumor promoters in mouse skin. By contrast, bryostatin-1 (bryo-1) isolated from marine bryozoan is a potent PKC activator with little tumor-promoting activity. Numerous investigations have suggested bryo-1 to be a promising therapeutic candidate for the above intractable diseases. However, there is a supply problem of bryo-1 both from natural sources and by organic synthesis. Recent approaches on the synthesis of bryo-1 have focused on its simplification, without decreasing the ability to activate PKC isozymes, to develop new medicinal leads. Another approach is to use the skeleton of natural PKC ligands to develop bryo-1 surrogates. We have recently identified 10-methyl-aplog-1 (26), a simplified analog of tumor-promoting Aplysiatoxin (ATX), as a possible therapeutic lead for cancer. This review summarizes recent investigations on the simplification of natural PKC ligands, bryo-1 and ATX, to develop potential medicinal leads.
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Improved and large-scale synthesis of 10-methyl-aplog-1, a potential lead for an anticancer drug
Tetrahedron, 2014Co-Authors: Masayuki Kikumori, Ryo C. Yanagita, Kazuhiro IrieAbstract:Abstract 10-Methyl-aplog-1 ( 1 ), a simplified analog of tumor-promoting Aplysiatoxin, is a potential lead for cancer therapy that exhibits marked and selective growth inhibitory effects against several human cancer cell lines and negligible tumor-promoting activity in vivo. However, more detailed evaluations of its toxicity and anticancer activity in vivo are hampered by supply problems associated with a non-optimal synthetic method. We here addressed this issue through a more practical and reliable synthetic method that afforded several hundred milligrams of 1 with high purity (>98%) in 23 steps from commercially available m -hydroxycinnamic acid with an overall yield of 1.1%. The utilization of two key reactions, substrate-controlled epoxidation and the oxidative cleavage of alkene with a free hydroxyl group, successfully reduced the existing five synthetic steps and markedly improved the handling of large amounts of intermediates. We also demonstrated for the first time that such an analog was synthetically accessible in reliable quantities and also that this large supply could advance in vivo trials for the treatment of cancer.
Masayuki Satake - One of the best experts on this subject based on the ideXlab platform.
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neo Aplysiatoxin a isolated from okinawan cyanobacterium moorea producens
Molecules, 2020Co-Authors: Mioko Kawaguchi, Yueyun Xiao, Masayuki Fukuoka, Hajime Uchida, Masayuki Satake, Botao Zhang, Hiroshi NagaiAbstract:A new Aplysiatoxin derivative, neo-Aplysiatoxin A (1), along with seven known compounds, neo-debromoAplysiatoxin A (2), dolastatin 3 (3), lyngbic acid (4), malyngamide M (5), hermitamide A (6), (−)-loliolide (7), and (+)-epiloliolide (8), was isolated from the Okinawan cyanobacterium Moorea producens. Their structures were elucidated on the basis of spectroscopic data, including high-resolution mass spectrometry and nuclear magnetic resonance. The compounds were evaluated for cytotoxic and diatom growth inhibition activities.
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Oscillatoxin I: A New Aplysiatoxin Derivative, from a Marine Cyanobacterium.
Toxins, 2019Co-Authors: Hiroshi Nagai, Mioko Kawaguchi, Hajime Uchida, Kazutaka Hayashi, Shingo Sato, Kaori Iida, Masayuki SatakeAbstract:Cyanobacteria have been shown to produce a number of bioactive compounds, including toxins. Some bioactive compounds obtained from a marine cyanobacterium Moorea producens (formerly Lyngbya majuscula) have been recognized as drug leads; one of these compounds is Aplysiatoxin. We have isolated various Aplysiatoxin derivatives from a M. producens sample obtained from the Okinawan coastal area. The frozen sample was extracted with organic solvents. The ethyl acetate layer was obtained from the crude extracts via liquid-liquid partitioning, then separated by HPLC using a reversed-phase column. Finally, 1.1 mg of the compound was isolated. The chemical structure of the isolated compound was elucidated with spectroscopic methods, using HR-MS and 1D and 2D NMR techniques, and was revealed to be oscillatoxin I, a new member of the Aplysiatoxin family. Oscillatoxin I showed cytotoxicity against the L1210 mouse lymphoma cell line and diatom growth-inhibition activity against the marine diatom Nitzschia amabilis.
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new Aplysiatoxin derivatives from the okinawan cyanobacterium moorea producens
Tetrahedron, 2019Co-Authors: Hiroshi Nagai, Minami Watanabe, Mioko Kawaguchi, Yueyun Xiao, Hajime Uchida, Ryuichi Watanabe, Kazutaka Hayashi, Shingo Sato, Masayuki SatakeAbstract:Abstract The marine cyanobacterium Moorea producens is a rich source of diverse compounds that possess a variety of biological activities. In the present study, eight new Aplysiatoxin derivatives, namely 6, 8–13, and 15, along with Aplysiatoxin (1), debromoAplysiatoxin (2), 3-methoxyAplysiatoxin (3), anhydroAplysiatoxin (4), anhydrodebromoAplysiatoxin (5), oscillatoxin B2 (7), and 30-methyloscillatoxin D (14) were isolated and identified from the Okinawan M. producens. In cytotoxicity and diatom growth inhibition tests, the fifteen compounds tested (1–15) showed moderate or no activity at a concentration of 10 μg/mL.
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Pathological effects of lyngbyatoxin A upon mice.
Toxicon, 2002Co-Authors: Masayuki Satake, Takeshi YasumotoAbstract:Abstract Histopathological changes induced in mice by lyngbyatoxin A were studied in connection with the occurrence of the toxin in marine turtles implicated in human intoxication. Lyngbyatoxin A showed an i.p. lethal dose 250 μg/kg in immature mice (3-week old) and most severely damaged capillaries of villi in the small intestine. Immature mice were more sensitive than matured ones and died of bleeding from the small intestines. With sublethal doses were observed erosion in the stomach, small intestine, cecum, and large intestine, as well as inflammation in the lung. Time course changes observed after p.o. administration of sublethal doses indicated severe mucus secretion and injuries to occur within 60 min in the intestine and within 24 h in the stomach. Increased inflammatory cells followed these injuries. The injuries in the lung, stomach, and small intestine took a few weeks for recovery. The cause of death and the effective dose levels resembled those of Aplysiatoxin poisoning.
Ryo C. Yanagita - One of the best experts on this subject based on the ideXlab platform.
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Synthesis and biological activities of simplified Aplysiatoxin analogs focused on the CH/π interaction.
Bioorganic & medicinal chemistry letters, 2020Co-Authors: Takumi Kobayashi, Ryo C. Yanagita, Kazuhiro IrieAbstract:Abstract DebromoAplysiatoxin (DAT) is a potent protein kinase C (PKC) activator with tumor-promoting and pro-inflammatory activities. Irie and colleagues have found that 10-methyl-aplog-1 (1), a simplified analog of DAT, has strong anti-proliferative activity against several cancer cell lines with few adverse effects. Therefore, 1 is a potential lead compound for cancer therapy. We synthesized a new derivative 2 which has a naphthalene ring at the side chain terminal position instead of a benzene ring, to increase CH/π interactions with Pro-241 of the PKCδ-C1B domain. Based on the synthetic route of 1, 2 was convergently synthesized in 26 linear steps from 6-hydroxy-1-naphthoic acid with an overall yield of 0.18%. Although the anti-proliferative activity of 2 was more potent than that of 1, the binding potency of 2 to the PKCδ-C1B domain did not exceed that of 1. Molecular dynamics simulation indicated the capability of 2 to simultaneously form hydrogen bonds and CH/π interactions with the PKCδ-C1B domain. Focusing on the hydrogen bonds, their geometry in the binding modes involving the CH/π interactions seemed to be sub-optimal, which may explain the slightly lower affinity of 2 compared to 1. This study could be of help in optimizing such interactions and synthesizing a promising lead cancer compound.
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Binding mode prediction of Aplysiatoxin, a potent agonist of protein kinase C, through molecular simulation and structure-activity study on simplified analogs of the receptor-recognition domain.
Bioorganic & medicinal chemistry, 2016Co-Authors: Yoshiki Ashida, Ryo C. Yanagita, Chise Takahashi, Yasuhiro Kawanami, Kazuhiro IrieAbstract:Abstract Aplysiatoxin (ATX) is a naturally occurring tumor promoter isolated from a sea hare and cyanobacteria. ATX binds to, and activates, protein kinase C (PKC) isozymes and shows anti-proliferative activity against human cancer cell lines. Recently, ATX has attracted attention as a lead compound for the development of novel anticancer drugs. In order to predict the binding mode between ATX and protein kinase Cδ (PKCδ) C1B domain, we carried out molecular docking simulation, atomistic molecular dynamics simulation in phospholipid membrane environment, and structure–activity study on a simple acyclic analog of ATX. These studies provided the binding model where the carbonyl group at position 27, the hydroxyl group at position 30, and the phenolic hydroxyl group at position 20 of ATX were involved in intermolecular hydrogen bonding with the PKCδ C1B domain, which would be useful for the rational design of ATX derivatives as anticancer lead compounds.
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Synthesis and biological activities of the amide derivative of aplog-1, a simplified analog of Aplysiatoxin with anti-proliferative and cytotoxic activities.
Bioscience biotechnology and biochemistry, 2015Co-Authors: Yusuke Hanaki, Harukuni Tokuda, Ryo C. Yanagita, Takahiro Sugahara, Misako Aida, Nobutaka Suzuki, Kazuhiro IrieAbstract:Aplog-1 is a simplified analog of the tumor-promoting Aplysiatoxin with anti-proliferative and cytotoxic activities against several cancer cell lines. Our recent findings have suggested that protein kinase Cδ (PKCδ) could be one of the target proteins of aplog-1. In this study, we synthesized amide-aplog-1 (3), in which the C-1 ester group was replaced with an amide group, to improve chemical stability in vivo. Unfortunately, 3 exhibited seventy-fold weaker binding affinity to the C1B domain of PKCδ than that of aplog-1, and negligible anti-proliferative and cytotoxic activities even at 10−4 M. A conformational analysis and density functional theory calculations indicated that the stable conformation of 3 differed from that of aplog-1. Since 27-methyl and 27-methoxy derivatives (1, 2) without the ability to bind to PKC isozymes exhibited marked anti-proliferative and cytotoxic activities at 10−4 M, 3 may be an inactive control to identify the target proteins of aplogs.
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synthesis and biological activities of simplified analogs of the natural pkc ligands bryostatin 1 and Aplysiatoxin
Chemical Record, 2014Co-Authors: Kazuhiro Irie, Ryo C. YanagitaAbstract:: Protein kinase C (PKC) isozymes play central roles in signal transduction on the cell surface and could serve as promising therapeutic targets of intractable diseases like cancer, Alzheimer's disease, and acquired immunodeficiency syndrome (AIDS). Although natural PKC ligands like phorbol esters, ingenol esters, and teleocidins have the potential to become therapeutic leads, most of them are potent tumor promoters in mouse skin. By contrast, bryostatin-1 (bryo-1) isolated from marine bryozoan is a potent PKC activator with little tumor-promoting activity. Numerous investigations have suggested bryo-1 to be a promising therapeutic candidate for the above intractable diseases. However, there is a supply problem of bryo-1 both from natural sources and by organic synthesis. Recent approaches on the synthesis of bryo-1 have focused on its simplification, without decreasing the ability to activate PKC isozymes, to develop new medicinal leads. Another approach is to use the skeleton of natural PKC ligands to develop bryo-1 surrogates. We have recently identified 10-methyl-aplog-1 (26), a simplified analog of tumor-promoting Aplysiatoxin (ATX), as a possible therapeutic lead for cancer. This review summarizes recent investigations on the simplification of natural PKC ligands, bryo-1 and ATX, to develop potential medicinal leads.
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Improved and large-scale synthesis of 10-methyl-aplog-1, a potential lead for an anticancer drug
Tetrahedron, 2014Co-Authors: Masayuki Kikumori, Ryo C. Yanagita, Kazuhiro IrieAbstract:Abstract 10-Methyl-aplog-1 ( 1 ), a simplified analog of tumor-promoting Aplysiatoxin, is a potential lead for cancer therapy that exhibits marked and selective growth inhibitory effects against several human cancer cell lines and negligible tumor-promoting activity in vivo. However, more detailed evaluations of its toxicity and anticancer activity in vivo are hampered by supply problems associated with a non-optimal synthetic method. We here addressed this issue through a more practical and reliable synthetic method that afforded several hundred milligrams of 1 with high purity (>98%) in 23 steps from commercially available m -hydroxycinnamic acid with an overall yield of 1.1%. The utilization of two key reactions, substrate-controlled epoxidation and the oxidative cleavage of alkene with a free hydroxyl group, successfully reduced the existing five synthetic steps and markedly improved the handling of large amounts of intermediates. We also demonstrated for the first time that such an analog was synthetically accessible in reliable quantities and also that this large supply could advance in vivo trials for the treatment of cancer.
Mioko Kawaguchi - One of the best experts on this subject based on the ideXlab platform.
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neo Aplysiatoxin a isolated from okinawan cyanobacterium moorea producens
Molecules, 2020Co-Authors: Mioko Kawaguchi, Yueyun Xiao, Masayuki Fukuoka, Hajime Uchida, Masayuki Satake, Botao Zhang, Hiroshi NagaiAbstract:A new Aplysiatoxin derivative, neo-Aplysiatoxin A (1), along with seven known compounds, neo-debromoAplysiatoxin A (2), dolastatin 3 (3), lyngbic acid (4), malyngamide M (5), hermitamide A (6), (−)-loliolide (7), and (+)-epiloliolide (8), was isolated from the Okinawan cyanobacterium Moorea producens. Their structures were elucidated on the basis of spectroscopic data, including high-resolution mass spectrometry and nuclear magnetic resonance. The compounds were evaluated for cytotoxic and diatom growth inhibition activities.
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Oscillatoxin I: A New Aplysiatoxin Derivative, from a Marine Cyanobacterium.
Toxins, 2019Co-Authors: Hiroshi Nagai, Mioko Kawaguchi, Hajime Uchida, Kazutaka Hayashi, Shingo Sato, Kaori Iida, Masayuki SatakeAbstract:Cyanobacteria have been shown to produce a number of bioactive compounds, including toxins. Some bioactive compounds obtained from a marine cyanobacterium Moorea producens (formerly Lyngbya majuscula) have been recognized as drug leads; one of these compounds is Aplysiatoxin. We have isolated various Aplysiatoxin derivatives from a M. producens sample obtained from the Okinawan coastal area. The frozen sample was extracted with organic solvents. The ethyl acetate layer was obtained from the crude extracts via liquid-liquid partitioning, then separated by HPLC using a reversed-phase column. Finally, 1.1 mg of the compound was isolated. The chemical structure of the isolated compound was elucidated with spectroscopic methods, using HR-MS and 1D and 2D NMR techniques, and was revealed to be oscillatoxin I, a new member of the Aplysiatoxin family. Oscillatoxin I showed cytotoxicity against the L1210 mouse lymphoma cell line and diatom growth-inhibition activity against the marine diatom Nitzschia amabilis.
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new Aplysiatoxin derivatives from the okinawan cyanobacterium moorea producens
Tetrahedron, 2019Co-Authors: Hiroshi Nagai, Minami Watanabe, Mioko Kawaguchi, Yueyun Xiao, Hajime Uchida, Ryuichi Watanabe, Kazutaka Hayashi, Shingo Sato, Masayuki SatakeAbstract:Abstract The marine cyanobacterium Moorea producens is a rich source of diverse compounds that possess a variety of biological activities. In the present study, eight new Aplysiatoxin derivatives, namely 6, 8–13, and 15, along with Aplysiatoxin (1), debromoAplysiatoxin (2), 3-methoxyAplysiatoxin (3), anhydroAplysiatoxin (4), anhydrodebromoAplysiatoxin (5), oscillatoxin B2 (7), and 30-methyloscillatoxin D (14) were isolated and identified from the Okinawan M. producens. In cytotoxicity and diatom growth inhibition tests, the fifteen compounds tested (1–15) showed moderate or no activity at a concentration of 10 μg/mL.
