The Experts below are selected from a list of 117 Experts worldwide ranked by ideXlab platform
Zhaohai Qin - One of the best experts on this subject based on the ideXlab platform.
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design and synthesis of novel hydrocarbylidene nitrohydrazinecarboximidamides against aphids based on natural product Galegine
Natural Product Research, 2021Co-Authors: Fenghai Zhao, Xiang Zhu, Ziyuan Zhou, Dongyan Yang, Zhaohai QinAbstract:A series of novel hydrocarbylidene nitrohydrazinecarboximidamides were designed and synthesized using an insecticidal natural product Galegine as a lead compound. The bioassay results show that the...
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synthesis and insecticidal activity of the fluorinated Galegine analogues
Natural Product Research, 2020Co-Authors: Jinlong Cai, Fenghai Zhao, Ziyuan Zhou, Dongyan Yang, Zhaohai QinAbstract:The introduction of fluorine atom can increase the biological activities of the target compounds remarkably. To find more safe and efficient insecticides, natural product Galegine as lead compound,...
Roger D Waigh - One of the best experts on this subject based on the ideXlab platform.
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benzylguanidines and other Galegine analogues inducing weight loss in mice
Journal of Medicinal Chemistry, 2009Co-Authors: Geoffrey D Coxon, Mark Mooney, B L Furman, Alan L Harvey, John Mctavish, Mahmoud Arastoo, Alan R Kennedy, Justice M Tettey, Roger D WaighAbstract:Dimethylallylguanidine, also known as Galegine, isolated from Galega officinalis, has been shown to have weight reducing properties in vivo. Substitution of the guanidine group with an N-cyano group and replacement of guanidine with amidine, pyrimidine, pyridine, or the imidazole moieties removed the weight reducing properties when evaluated in BALB/c mice. However, retention of the guanidine and replacement of the dimethylallyl group by a series of functionalized benzyl substituents was shown to exhibit, and in some cases significantly improve, the weight reducing properties of these molecules in BALB/c, ob/ob, and diet induced obesity (DIO) mice models. The lead compound identified, across all models, was 1-(4-chlorobenzyl)guanidine hemisulfate, which gave an average daily weight difference (% from time-matched controls; +/- SEM) of -19.7 +/- 1.0, -11.0 +/- 0.7, and -7.3 +/- 0.8 in BALB/c, ob/ob, and DIO models, respectively.
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mechanisms underlying the metabolic actions of Galegine that contribute to weight loss in mice
British Journal of Pharmacology, 2008Co-Authors: Mark Mooney, Simon A. Hawley, Sarah Fogarty, C Stevenson, Alison M Gallagher, P Palit, D G Hardie, Geoffrey D Coxon, Roger D Waigh, Rothwelle J TateAbstract:Galegine and guanidine, originally isolated from Galega officinalis, led to the development of the biguanides. The weight-reducing effects of Galegine have not previously been studied and the present investigation was undertaken to determine its mechanism(s) of action. Body weight and food intake were examined in mice. Glucose uptake and acetyl-CoA carboxylase activity were studied in 3T3-L1 adipocytes and L6 myotubes and AMP activated protein kinase (AMPK) activity was examined in cell lines. The gene expression of some enzymes involved in fat metabolism was examined in 3T3-L1 adipocytes. Galegine administered in the diet reduced body weight in mice. Pair-feeding indicated that at least part of this effect was independent of reduced food intake. In 3T3-L1 adipocytes and L6 myotubes, Galegine (50 mM-3mM) stimulated glucose uptake. Galegine (1-300 mM) also reduced isoprenaline-mediated lipolysis in 3T3-L1 adipocytes and inhibited acetyl-CoA carboxylase activity in 3T3-L1 adipocytes and L6 myotubes. Galegine (500 mM) down-regulated genes concerned with fatty acid synthesis, including fatty acid synthase and its upstream regulator SREBP. Galegine (10 mM and above) produced a concentration-dependent activation of AMP activated protein kinase (AMPK) in H4IIE rat hepatoma, HEK293 human kidney cells, 3T3-L1 adipocytes and L6 myotubes. Activation of AMPK can explain many of the effects of Galegine, including enhanced glucose uptake and inhibition of acetyl-CoA carboxylase. Inhibition of acetyl-CoA carboxylase both inhibits fatty acid synthesis and stimulates fatty acid oxidation, and this may to contribute to the in vivo effect of Galegine on body weight.
Regasini, Luis Octavio - One of the best experts on this subject based on the ideXlab platform.
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Human ABCB1 confers cells resistance to cytotoxic guanidine alkaloids from Pterogyne nitens
Ios Press, 2015Co-Authors: Satake Kazuhiro, Mitani Yuji, Regasini, Luis Octavio, Bolzani, Vanderlan Da Silva, Efferth Thomas, Tsukamoto Megumi, Nakagawa HiroshiAbstract:Multidrug resistance (MDR) caused by human ABCB1 (P-glycoprotein/MDR1) is one of the major obstacles in chemotherapy. To understand the mechanism of MDR by ABCB1 and circumvent the MDR, in the present study, we established human ABCB1-expressing cells (Flp-In-293/ABCB1 cells) and examined the cytotoxic effects of four guanidine alkaloids from Pterogyne nitens (Galegine, nitensidine A, pterogynidine and pterogynine) using Flp-In-293/Mock and Flp-In-293/ABCB1 cells. The activity of ABCB1 in Flp-In-293/ABCB1 cells were confirmed by typical substrates for ABCB1 (taxol and vinblastine) in MTT assay. Flp-In-293/ABCB1 cells were also resistant to the four guanidine alkaloids as well as taxol and vinblastine compared to Flp-In-293/Mock cells although the four guanidine alkaloids exhibited cytotoxicity against the two Flp-In-293 cells. Furthermore, the four guanidine alkaloids were also found to stimulate the ATPase activity of ABCB1 in ATPase assays. These results suggest that ABCB1 can confer the resistance to the cytotoxic guanidine alkaloids by transporting them.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP
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In Vitro Antibacterial Activity of Prenylated Guanidine Alkaloids from Pterogyne nitens and Synthetic Analogues
Amer Chemical Soc, 2014Co-Authors: Coqueiro Aline, Regasini, Luis Octavio, Bolzani, Vanderlan Da Silva, Stapleton Paul, Gibbons SimonAbstract:The present investigation deals with the antibiotic activity of eight natural guanidine alkaloids and two synthetic analogues against a variety of clinically relevant methicillin-resistant Staphylococcus aureus strains. Galegine (1) and pterogynidine (2) were the most potent compounds, with a minimum inhibitory concentration of 4 mg/L, to all tested strains. The preliminary chemical features correlating to anti-MRSA activity showed that the size of the side chain and the substitution pattern in the guanidine core played a key role in the antibacterial activity of the imino group. Guanidine alkaloids 1 and 2 are promising molecular models for further synthetic derivatives and, thus, for medicinal chemistry studies.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES
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In vitro antibacterial activity of prenylated guanidine alkaloids from Pterogyne nitens and synthetic analogues
'American Chemical Society (ACS)', 2014Co-Authors: Coqueiro Aline, Regasini, Luis Octavio, Stapleton Paul, Da Silva Bolzani Vanderlan, Gibbons SimonAbstract:The present investigation deals with the antibiotic activity of eight natural guanidine alkaloids and two synthetic analogues against a variety of clinically relevant methicillin-resistant Staphylococcus aureus strains. Galegine (1) and pterogynidine (2) were the most potent compounds, with a minimum inhibitory concentration of 4 mg/L, to all tested strains. The preliminary chemical features correlating to anti-MRSA activity showed that the size of the side chain and the substitution pattern in the guanidine core played a key role in the antibacterial activity of the imino group. Guanidine alkaloids 1 and 2 are promising molecular models for further synthetic derivatives and, thus, for medicinal chemistry studies
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Nitensidine A, a guanidine alkaloid from Pterogyne nitens, is a novel substrate for human ABC transporter ABCB1
2013Co-Authors: Tajima Yasuhiro, Murase Hayato, Satake Kazuhiro, Mitani Yuji, Regasini, Luis Octavio, Bolzani, Vanderlan Da Silva, Nakagawa Hiroshi, Ai Tamura, Kadioglu Onat, Ishikawa ToshihisaAbstract:The Pterogyne nitens (Fabaceae) tree, native to South America, has been found to produce guanidine alkaloids as well as bioactive flavonols such as kaempferol, quercetin, and rutin. In the present study, we examined the possibility of interaction between human ATP-binding cassette (ABC) transporter ABCB1 and four guanidine alkaloids isolated from P. nitens (i.e., Galegine, nitensidine A, pterogynidine, and pterogynine) using human T cell lymphoblast-like leukemia cell line CCRF-CEM and its multi-drug resistant (MDR) counterpart CEM/ADR5000. In XTT assays, CEM/ADR5000 cells were resistant to the four guanidine alkaloids compared to CCRF-CEM cells, although the four guanidine alkaloids exhibited some level of cytotoxicity against both CCRF-CEM and CEM/ADR5000 cells. In ATPase assays, three of the four guanidine alkaloids were found to stimulate the ATPase activity of ABCB1. Notably, nitensidine A was clearly found to stimulate the ATPase activity of ABCB1 as strongly as the control drug, verapamil. Furthermore, the cytotoxic effect of nitensidine A on CEM/ADR5000 cells was synergistically enhanced by verapamil. Nitensidine A inhibited the extrusion of calcein by ABCB1. In the present study, the possibility of interaction between ABCB1 and two synthetic nitensidine A analogs (nitensidine AT and AU) were examined to gain insight into the mechanism by which nitensidine A stimulates the ATPase activity of ABCB1. The ABCB1-dependent ATPase activity stimulated by nitensidine A was greatly reduced by substituting sulfur (S) or oxygen (O) for the imino nitrogen atom (N) in nitensidine A. Molecular docking studies on human ABCB1 showed that, guanidine alkaloids from P. nitens dock to the same binding pocket as verapamil. Nitensidine A and its analogs exhibit similar binding energies to verapamil. Taken together, this research clearly indicates that nitensidine A is a novel substrate for ABCB1. The present results also suggest that the number, binding site, and polymerization degree of the isoprenyl moiety in the guanidine alkaloids and the imino nitrogen atom cooperatively contribute to their stimulation of ABCB1's ATPase activity. © 2013 Elsevier GmbH. All rights reserved
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Nitensidine A, a guanidine alkaloid from Pterogyne nitens, induces osteoclastic cell death
2013Co-Authors: Tajima Yasuhiro, Murase Hayato, Satake Kazuhiro, Mitani Yuji, Regasini, Luis Octavio, Bolzani, Vanderlan Da Silva, Efferth Thomas, Nakagawa HiroshiAbstract:Nitensidine A is a guanidine alkaloid isolated from Pterogyne nitens, a common plant in South America. To gain insight into the biological activity of P. nitens-produced compounds, we examined herein their biological effects on osteoclasts, multinucleated giant cells that regulate bone metabolism by resorbing bone. Among four guanidine alkaloids (i.e., Galegine, nitensidine A, pterogynidine, and pterogynine), nitensidine A and pterogynine exhibited anti-osteoclastic effects at 10 μM by reducing the number of osteoclasts on the culture plate whereas Galegine and pterogynidine did not. The anti-osteoclastic activities of nitensidine A and pterogynine were exerted in a concentration-dependent manner, whereas nitensidine A exhibited an approximate threefold stronger effect than pterogynine (IC50 values: nitensidine A, 0.93 ± 0.024 μM; pterogynine, 2.7 ± 0.40 μM). In the present study, the anti-osteoclastic effects of two synthetic nitensidine A derivatives (nitensidine AT and AU) were also examined to gain insight into the structural features of nitensidine A that exert an anti-osteoclastic effect. The anti-osteoclastic effect of nitensidine A was greatly reduced by substituting the imino nitrogen atom in nitensidine A with sulfur or oxygen. According to the differences in chemical structures and anti-osteoclastic effects of the four guanidine alkaloids and the two synthetic nitensidine A derivatives, it is suggested that the number, binding site, and polymerization degree of isoprenyl moiety in the guanidine alkaloids and the imino nitrogen atom cooperatively contribute to their anti-osteoclastic effects. © 2013 Springer Science+Business Media Dordrecht
Mark Mooney - One of the best experts on this subject based on the ideXlab platform.
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benzylguanidines and other Galegine analogues inducing weight loss in mice
Journal of Medicinal Chemistry, 2009Co-Authors: Geoffrey D Coxon, Mark Mooney, B L Furman, Alan L Harvey, John Mctavish, Mahmoud Arastoo, Alan R Kennedy, Justice M Tettey, Roger D WaighAbstract:Dimethylallylguanidine, also known as Galegine, isolated from Galega officinalis, has been shown to have weight reducing properties in vivo. Substitution of the guanidine group with an N-cyano group and replacement of guanidine with amidine, pyrimidine, pyridine, or the imidazole moieties removed the weight reducing properties when evaluated in BALB/c mice. However, retention of the guanidine and replacement of the dimethylallyl group by a series of functionalized benzyl substituents was shown to exhibit, and in some cases significantly improve, the weight reducing properties of these molecules in BALB/c, ob/ob, and diet induced obesity (DIO) mice models. The lead compound identified, across all models, was 1-(4-chlorobenzyl)guanidine hemisulfate, which gave an average daily weight difference (% from time-matched controls; +/- SEM) of -19.7 +/- 1.0, -11.0 +/- 0.7, and -7.3 +/- 0.8 in BALB/c, ob/ob, and DIO models, respectively.
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mechanisms underlying the metabolic actions of Galegine that contribute to weight loss in mice
British Journal of Pharmacology, 2008Co-Authors: Mark Mooney, Simon A. Hawley, Sarah Fogarty, C Stevenson, Alison M Gallagher, P Palit, D G Hardie, Geoffrey D Coxon, Roger D Waigh, Rothwelle J TateAbstract:Galegine and guanidine, originally isolated from Galega officinalis, led to the development of the biguanides. The weight-reducing effects of Galegine have not previously been studied and the present investigation was undertaken to determine its mechanism(s) of action. Body weight and food intake were examined in mice. Glucose uptake and acetyl-CoA carboxylase activity were studied in 3T3-L1 adipocytes and L6 myotubes and AMP activated protein kinase (AMPK) activity was examined in cell lines. The gene expression of some enzymes involved in fat metabolism was examined in 3T3-L1 adipocytes. Galegine administered in the diet reduced body weight in mice. Pair-feeding indicated that at least part of this effect was independent of reduced food intake. In 3T3-L1 adipocytes and L6 myotubes, Galegine (50 mM-3mM) stimulated glucose uptake. Galegine (1-300 mM) also reduced isoprenaline-mediated lipolysis in 3T3-L1 adipocytes and inhibited acetyl-CoA carboxylase activity in 3T3-L1 adipocytes and L6 myotubes. Galegine (500 mM) down-regulated genes concerned with fatty acid synthesis, including fatty acid synthase and its upstream regulator SREBP. Galegine (10 mM and above) produced a concentration-dependent activation of AMP activated protein kinase (AMPK) in H4IIE rat hepatoma, HEK293 human kidney cells, 3T3-L1 adipocytes and L6 myotubes. Activation of AMPK can explain many of the effects of Galegine, including enhanced glucose uptake and inhibition of acetyl-CoA carboxylase. Inhibition of acetyl-CoA carboxylase both inhibits fatty acid synthesis and stimulates fatty acid oxidation, and this may to contribute to the in vivo effect of Galegine on body weight.
Geoffrey D Coxon - One of the best experts on this subject based on the ideXlab platform.
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benzylguanidines and other Galegine analogues inducing weight loss in mice
Journal of Medicinal Chemistry, 2009Co-Authors: Geoffrey D Coxon, Mark Mooney, B L Furman, Alan L Harvey, John Mctavish, Mahmoud Arastoo, Alan R Kennedy, Justice M Tettey, Roger D WaighAbstract:Dimethylallylguanidine, also known as Galegine, isolated from Galega officinalis, has been shown to have weight reducing properties in vivo. Substitution of the guanidine group with an N-cyano group and replacement of guanidine with amidine, pyrimidine, pyridine, or the imidazole moieties removed the weight reducing properties when evaluated in BALB/c mice. However, retention of the guanidine and replacement of the dimethylallyl group by a series of functionalized benzyl substituents was shown to exhibit, and in some cases significantly improve, the weight reducing properties of these molecules in BALB/c, ob/ob, and diet induced obesity (DIO) mice models. The lead compound identified, across all models, was 1-(4-chlorobenzyl)guanidine hemisulfate, which gave an average daily weight difference (% from time-matched controls; +/- SEM) of -19.7 +/- 1.0, -11.0 +/- 0.7, and -7.3 +/- 0.8 in BALB/c, ob/ob, and DIO models, respectively.
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mechanisms underlying the metabolic actions of Galegine that contribute to weight loss in mice
British Journal of Pharmacology, 2008Co-Authors: Mark Mooney, Simon A. Hawley, Sarah Fogarty, C Stevenson, Alison M Gallagher, P Palit, D G Hardie, Geoffrey D Coxon, Roger D Waigh, Rothwelle J TateAbstract:Galegine and guanidine, originally isolated from Galega officinalis, led to the development of the biguanides. The weight-reducing effects of Galegine have not previously been studied and the present investigation was undertaken to determine its mechanism(s) of action. Body weight and food intake were examined in mice. Glucose uptake and acetyl-CoA carboxylase activity were studied in 3T3-L1 adipocytes and L6 myotubes and AMP activated protein kinase (AMPK) activity was examined in cell lines. The gene expression of some enzymes involved in fat metabolism was examined in 3T3-L1 adipocytes. Galegine administered in the diet reduced body weight in mice. Pair-feeding indicated that at least part of this effect was independent of reduced food intake. In 3T3-L1 adipocytes and L6 myotubes, Galegine (50 mM-3mM) stimulated glucose uptake. Galegine (1-300 mM) also reduced isoprenaline-mediated lipolysis in 3T3-L1 adipocytes and inhibited acetyl-CoA carboxylase activity in 3T3-L1 adipocytes and L6 myotubes. Galegine (500 mM) down-regulated genes concerned with fatty acid synthesis, including fatty acid synthase and its upstream regulator SREBP. Galegine (10 mM and above) produced a concentration-dependent activation of AMP activated protein kinase (AMPK) in H4IIE rat hepatoma, HEK293 human kidney cells, 3T3-L1 adipocytes and L6 myotubes. Activation of AMPK can explain many of the effects of Galegine, including enhanced glucose uptake and inhibition of acetyl-CoA carboxylase. Inhibition of acetyl-CoA carboxylase both inhibits fatty acid synthesis and stimulates fatty acid oxidation, and this may to contribute to the in vivo effect of Galegine on body weight.
