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Tess Astatkie - One of the best experts on this subject based on the ideXlab platform.
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Podophyllotoxin and essential oil profile of juniperus and related species
Industrial Crops and Products, 2013Co-Authors: Charles L. Cantrell, Valtcho D. Zheljazkov, Weste L.a. Osbrink, Amaya Castro, Victor Maddox, Lyle E. Craker, Tess AstatkieAbstract:Podophyllotoxin is currently in high demand as the lead chemical precursor for the anti-cancer drugs etoposide and teniposide. We conducted a two-phase study: (i) screening of Juniperus and other related species and identified Juniperus virginiana as the species with the highest Podophyllotoxin concentration and (ii) established the limits of variations of Podophyllotoxin and essential oil content and composition in J. virginiana in the United States. In the second phase of the study, J. virginiana trees at 49 locations in Mississippi, Alabama, Tennessee, and North Dakota were sampled and analyzed for both Podophyllotoxin and essential oil. Both the essential oil and Podophyllotoxin had similar concentration ranges as percent of dry J. virginiana leaves. Hence the following qualitative grouping with respect to concentration of natural products in the leaves was assigned: very high (>0.3%), high (0.2–0.3%), medium (0.1–0.2%), and low (<0.1%). Based on the above qualitative grouping, the J. virginiana accession were divided into 10 different groups (chemotypes). The J. virginiana accessions also differed in essential oil composition, with wide variation of individual constituents. Based on the essential oil composition, the J. virginiana accessions were divided into the following groups (chemotypes): (1) safrole–limonene–linalool; (2) safrole–β-pinene–limonene–linalool; (3) β-pinene–limonene; (4) limonene; (5) limonene–linalool; (6) limonene–safrole; (7) limonene–safrole–β-pinene; (8) β-pinene–limonene–bornyl acetate; (9) β-pinene–limonene–linalool–bornyl acetate; and (10) myrcene–limonene chemotype. The essential oil of two of the J. virginiana chemotypes showed differential antioxidant activity. J. virginiana leaves, a by-product from the timber industry could be used as a sustainable source for both Podophyllotoxin and essential oil. The availability of various chemotypes offers an opportunity for the development of cultivars for commercial production of Podophyllotoxin and essential oil with specific compositional profile to meet the market requirements.
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Bioprospecting for Podophyllotoxin in the Big Horn Mountains, Wyoming
Industrial Crops and Products, 2013Co-Authors: Valtcho D. Zheljazkov, Charles L. Cantrell, Mateus Augusto Donega, Tess AstatkieAbstract:Abstract The objective of this study was to evaluate variations in Podophyllotoxin concentrations in Juniperus species found in the Big Horn Mountains in Wyoming. It was found that Juniperus species in the Big Horn Mountains included three species; J. communis L. (common juniper), J. horizontalis Moench. (creeping juniper) and J. scopulorum Sarg. (Rocky Mountain juniper). Of these species, none of the 12 accessions of J. communis contained detectable amounts of Podophyllotoxin. All accessions of J. scopulorum but one contained Podophyllotoxin. Podophyllotoxin concentration in J. horizontalis and J. scopulorum did not correlate to the elevation of the selection sites. The concentration of Podophyllotoxin in J. scopulorum ranged from 0 to 0.40%, while the concentration of Podophyllotoxin in J. horizontalis ranged from 0.27 to 0.73%. Overall, J. horizontalis accessions in the Big Horn Mountains showed higher concentration of Podophyllotoxin than the one in J. scopulorum. The range of concentrations in Podophyllotoxin in J. horizontalis and J. scopulorum in the Big Horn Mountains were within the range or (in case of J. horizontalis), much higher than the ones reported previously for J. virginiana. This is the first report on Podophyllotoxin in J. horizontalis. The concentrations of Podophyllotoxin in some accessions of J. horizontalis were twice as high as the ones reported previously for any other junipers. This study demonstrated that Juniperus species in the Big Horn Mountains have a potential to be used as a source for Podophyllotoxin.
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Podophyllotoxin and essential oil profile of Juniperus and related species
Industrial Crops and Products, 2013Co-Authors: Charles L. Cantrell, Valtcho D. Zheljazkov, Weste L.a. Osbrink, Amaya Castro, Victor Maddox, Lyle E. Craker, Tess AstatkieAbstract:Podophyllotoxin is currently in high demand as the lead chemical precursor for the anti-cancer drugs etoposide and teniposide. We conducted a two-phase study: (i) screening of Juniperus and other related species and identified Juniperus virginiana as the species with the highest Podophyllotoxin concentration and (ii) established the limits of variations of Podophyllotoxin and essential oil content and composition in J. virginiana in the United States. In the second phase of the study, J. virginiana trees at 49 locations in Mississippi, Alabama, Tennessee, and North Dakota were sampled and analyzed for both Podophyllotoxin and essential oil. Both the essential oil and Podophyllotoxin had similar concentration ranges as percent of dry J. virginiana leaves. Hence the following qualitative grouping with respect to concentration of natural products in the leaves was assigned: very high (>0.3%), high (0.2–0.3%), medium (0.1–0.2%), and low (
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Podophyllotoxin Concentration in Junipers in the Big Horn Mountains in Wyoming
HortScience, 2012Co-Authors: Valtcho D. Zheljazkov, Charles L. Cantrell, Tess Astatkie, Mateus Augusto Donega, Bonnie HeidelAbstract:Podophyllotoxin is used for the production of the anticancer drugs etoposide, etopophos, and teniposide. Currently, Podophyllotoxin is extracted from the Himalayan mayapple (Podophyllum hexandrum Royle). Some junipers and other species also contain the same natural product and have been explored as a domestic source for this compound. The objective of this study was to screen junipers in the Big Horn Mountains in Wyoming for Podophyllotoxin. Twenty junipers (18 accessions of Juniperus horizontalis Moench. and two accessions of J. scopulorum Sarg.) were sampled in Mar. 2012 and analyzed for Podophyllotoxin. Podophyllotoxin concentration in the samples varied from 0.058% to 0.673% with five accessions having podophylloxin concentration above 0.5%. This study demonstrated wide variation of Podophyllotoxin in J. horizontalis and J. scopulorum in the Big Horn Mountains. Some of the accessions had greater than 0.5% Podophyllotoxin making them a feasible source for Podophyllotoxin extraction.
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Variation in Podophyllotoxin concentration in leaves and rhizomes of American mayapple (Podophyllum peltatum L.)
Industrial Crops and Products, 2011Co-Authors: Valtcho D. Zheljazkov, Charles L. Cantrell, Tess AstatkieAbstract:Abstract Podophyllotoxin is a precursor for compounds used in the synthesis of commercially available anticancer drugs and their precursors etoposide, teniposide, and etopophos. Podophyllotoxin is currently obtained from the underground plant parts (roots and rhizomes) of Himalayan mayapple ( Podophyllum emodii Wall.) but is also found in several other species, including American mayapple. There is no information in the literature on Podophyllotoxin concentration in the roots or rhizomes of the American mayapple, and it was not clear if Podophyllotoxin concentration in underground plant parts is correlated with the concentration in aboveground plant parts. The objective of this study was to estimate Podophyllotoxin concentration in the leaves and rhizomes of 28 accessions of American mayapple under natural conditions (wild) and compare this to Podophyllotoxin concentrations of the same accessions in the leaves when cultivated. Podophyllotoxin concentration in the rhizomes was positively correlated to soil organic matter content and to the concentrations of soil-available P and Na. Podophyllotoxin in the leaves was negatively correlated to soil-available Mg concentrations. The concentration of Podophyllotoxin in the leaves varied from undetectable amounts to 2.52%, whereas Podophyllotoxin in rhizomes varied from 0.14% to 0.42%. Most of the accessions had greater than 0.45% Podophyllotoxin concentration in the leaves under both wild and cultivated conditions. There was no significant correlation between the Podophyllotoxin concentrations in rhizomes and leaves; nine accessions had the highest Podophyllotoxin concentration in leaves under natural environment. Another nine accessions had the highest Podophyllotoxin in the leaves under cultivated conditions, and an additional eight accessions had greater Podophyllotoxin concentrations in roots than in leaves irrespective of the environment. The results from this study may contribute toward developing American mayapple into a new cash crop for U.S. farmers.
Valtcho D. Zheljazkov - One of the best experts on this subject based on the ideXlab platform.
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Podophyllotoxin and essential oil profile of juniperus and related species
Industrial Crops and Products, 2013Co-Authors: Charles L. Cantrell, Valtcho D. Zheljazkov, Weste L.a. Osbrink, Amaya Castro, Victor Maddox, Lyle E. Craker, Tess AstatkieAbstract:Podophyllotoxin is currently in high demand as the lead chemical precursor for the anti-cancer drugs etoposide and teniposide. We conducted a two-phase study: (i) screening of Juniperus and other related species and identified Juniperus virginiana as the species with the highest Podophyllotoxin concentration and (ii) established the limits of variations of Podophyllotoxin and essential oil content and composition in J. virginiana in the United States. In the second phase of the study, J. virginiana trees at 49 locations in Mississippi, Alabama, Tennessee, and North Dakota were sampled and analyzed for both Podophyllotoxin and essential oil. Both the essential oil and Podophyllotoxin had similar concentration ranges as percent of dry J. virginiana leaves. Hence the following qualitative grouping with respect to concentration of natural products in the leaves was assigned: very high (>0.3%), high (0.2–0.3%), medium (0.1–0.2%), and low (<0.1%). Based on the above qualitative grouping, the J. virginiana accession were divided into 10 different groups (chemotypes). The J. virginiana accessions also differed in essential oil composition, with wide variation of individual constituents. Based on the essential oil composition, the J. virginiana accessions were divided into the following groups (chemotypes): (1) safrole–limonene–linalool; (2) safrole–β-pinene–limonene–linalool; (3) β-pinene–limonene; (4) limonene; (5) limonene–linalool; (6) limonene–safrole; (7) limonene–safrole–β-pinene; (8) β-pinene–limonene–bornyl acetate; (9) β-pinene–limonene–linalool–bornyl acetate; and (10) myrcene–limonene chemotype. The essential oil of two of the J. virginiana chemotypes showed differential antioxidant activity. J. virginiana leaves, a by-product from the timber industry could be used as a sustainable source for both Podophyllotoxin and essential oil. The availability of various chemotypes offers an opportunity for the development of cultivars for commercial production of Podophyllotoxin and essential oil with specific compositional profile to meet the market requirements.
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Bioprospecting for Podophyllotoxin in the Big Horn Mountains, Wyoming
Industrial Crops and Products, 2013Co-Authors: Valtcho D. Zheljazkov, Charles L. Cantrell, Mateus Augusto Donega, Tess AstatkieAbstract:Abstract The objective of this study was to evaluate variations in Podophyllotoxin concentrations in Juniperus species found in the Big Horn Mountains in Wyoming. It was found that Juniperus species in the Big Horn Mountains included three species; J. communis L. (common juniper), J. horizontalis Moench. (creeping juniper) and J. scopulorum Sarg. (Rocky Mountain juniper). Of these species, none of the 12 accessions of J. communis contained detectable amounts of Podophyllotoxin. All accessions of J. scopulorum but one contained Podophyllotoxin. Podophyllotoxin concentration in J. horizontalis and J. scopulorum did not correlate to the elevation of the selection sites. The concentration of Podophyllotoxin in J. scopulorum ranged from 0 to 0.40%, while the concentration of Podophyllotoxin in J. horizontalis ranged from 0.27 to 0.73%. Overall, J. horizontalis accessions in the Big Horn Mountains showed higher concentration of Podophyllotoxin than the one in J. scopulorum. The range of concentrations in Podophyllotoxin in J. horizontalis and J. scopulorum in the Big Horn Mountains were within the range or (in case of J. horizontalis), much higher than the ones reported previously for J. virginiana. This is the first report on Podophyllotoxin in J. horizontalis. The concentrations of Podophyllotoxin in some accessions of J. horizontalis were twice as high as the ones reported previously for any other junipers. This study demonstrated that Juniperus species in the Big Horn Mountains have a potential to be used as a source for Podophyllotoxin.
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Podophyllotoxin and essential oil profile of Juniperus and related species
Industrial Crops and Products, 2013Co-Authors: Charles L. Cantrell, Valtcho D. Zheljazkov, Weste L.a. Osbrink, Amaya Castro, Victor Maddox, Lyle E. Craker, Tess AstatkieAbstract:Podophyllotoxin is currently in high demand as the lead chemical precursor for the anti-cancer drugs etoposide and teniposide. We conducted a two-phase study: (i) screening of Juniperus and other related species and identified Juniperus virginiana as the species with the highest Podophyllotoxin concentration and (ii) established the limits of variations of Podophyllotoxin and essential oil content and composition in J. virginiana in the United States. In the second phase of the study, J. virginiana trees at 49 locations in Mississippi, Alabama, Tennessee, and North Dakota were sampled and analyzed for both Podophyllotoxin and essential oil. Both the essential oil and Podophyllotoxin had similar concentration ranges as percent of dry J. virginiana leaves. Hence the following qualitative grouping with respect to concentration of natural products in the leaves was assigned: very high (>0.3%), high (0.2–0.3%), medium (0.1–0.2%), and low (
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Podophyllotoxin Concentration in Junipers in the Big Horn Mountains in Wyoming
HortScience, 2012Co-Authors: Valtcho D. Zheljazkov, Charles L. Cantrell, Tess Astatkie, Mateus Augusto Donega, Bonnie HeidelAbstract:Podophyllotoxin is used for the production of the anticancer drugs etoposide, etopophos, and teniposide. Currently, Podophyllotoxin is extracted from the Himalayan mayapple (Podophyllum hexandrum Royle). Some junipers and other species also contain the same natural product and have been explored as a domestic source for this compound. The objective of this study was to screen junipers in the Big Horn Mountains in Wyoming for Podophyllotoxin. Twenty junipers (18 accessions of Juniperus horizontalis Moench. and two accessions of J. scopulorum Sarg.) were sampled in Mar. 2012 and analyzed for Podophyllotoxin. Podophyllotoxin concentration in the samples varied from 0.058% to 0.673% with five accessions having podophylloxin concentration above 0.5%. This study demonstrated wide variation of Podophyllotoxin in J. horizontalis and J. scopulorum in the Big Horn Mountains. Some of the accessions had greater than 0.5% Podophyllotoxin making them a feasible source for Podophyllotoxin extraction.
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Variation in Podophyllotoxin concentration in leaves and rhizomes of American mayapple (Podophyllum peltatum L.)
Industrial Crops and Products, 2011Co-Authors: Valtcho D. Zheljazkov, Charles L. Cantrell, Tess AstatkieAbstract:Abstract Podophyllotoxin is a precursor for compounds used in the synthesis of commercially available anticancer drugs and their precursors etoposide, teniposide, and etopophos. Podophyllotoxin is currently obtained from the underground plant parts (roots and rhizomes) of Himalayan mayapple ( Podophyllum emodii Wall.) but is also found in several other species, including American mayapple. There is no information in the literature on Podophyllotoxin concentration in the roots or rhizomes of the American mayapple, and it was not clear if Podophyllotoxin concentration in underground plant parts is correlated with the concentration in aboveground plant parts. The objective of this study was to estimate Podophyllotoxin concentration in the leaves and rhizomes of 28 accessions of American mayapple under natural conditions (wild) and compare this to Podophyllotoxin concentrations of the same accessions in the leaves when cultivated. Podophyllotoxin concentration in the rhizomes was positively correlated to soil organic matter content and to the concentrations of soil-available P and Na. Podophyllotoxin in the leaves was negatively correlated to soil-available Mg concentrations. The concentration of Podophyllotoxin in the leaves varied from undetectable amounts to 2.52%, whereas Podophyllotoxin in rhizomes varied from 0.14% to 0.42%. Most of the accessions had greater than 0.45% Podophyllotoxin concentration in the leaves under both wild and cultivated conditions. There was no significant correlation between the Podophyllotoxin concentrations in rhizomes and leaves; nine accessions had the highest Podophyllotoxin concentration in leaves under natural environment. Another nine accessions had the highest Podophyllotoxin in the leaves under cultivated conditions, and an additional eight accessions had greater Podophyllotoxin concentrations in roots than in leaves irrespective of the environment. The results from this study may contribute toward developing American mayapple into a new cash crop for U.S. farmers.
Niesko Pras - One of the best experts on this subject based on the ideXlab platform.
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Plant cell factories as a source for anti-cancer lignans
Phytochemistry Reviews, 2002Co-Authors: R.r.j. Arroo, Niesko Pras, A. W. Alfermann, Maike Petersen, M. Medarde, J.g. WoolleyAbstract:The review places Podophyllotoxin, a powerful anti-cancer material used in clinical treatment of small cell cancers, in focus. The economical synthesis of Podophyllotoxin is not feasible and demand for this material outstrips supply. At present, Podophyllum hexandrum (Indian May apple) is the commercial source but it grows in an inhospitable region (the Himalayas) where it is collected from wild stands. Furthermore, the plant is now an endangered species. Alternative sources of Podophyllotoxin are considered, e.g., the supply of Podophyllotoxin and related lignans by establishing plant cell cultures that can be grown in fermentation vessels. Increase of product yields, by variation of medium and culture conditions or by varying the channelling of precursors into side-branches of the biosynthetic pathway by molecular approaches, are discussed.
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The use of plant cell cultures for the production of Podophyllotoxin and related lignans
Journal of Applied Botany-angewandte Botanik, 2000Co-Authors: U Empt, Niesko Pras, A. W. Alfermann, Maike PetersenAbstract:Podophyllotoxin isolated from rhizomes of Podophyllum plants (Podophyllaceae) serves as precursor for the semi-synthesis of anticancer therapeutics. The plants are collected from the wild and are becoming threatened species due to overcollection. Suspension cultures of Linum album (Linaceae) accumulate Podophyllotoxin as well and could therefore serve as an alternative source for this important aryltetralin lactone lignin. The culture characteristics of suspension cultures of Linum album are reported in the paper. The fast growth of the cell culture and a Podophyllotoxin accumulation of about 0.2% of the cell dry weight would enable a Podophyllotoxin production of ca. 28 mg in 1 1 days in one liter of suspension culture.
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GLUCOSYLATION OF CYCLODEXTRIN-COMPLEXED Podophyllotoxin BY CELL-CULTURES OF LINUM-FLAVUM L
Plant Cell Tissue and Organ Culture, 1993Co-Authors: Wim Van Uden, Holidi Oeij, Herman J. Woerdenbag, Niesko PrasAbstract:The glucosylation of the cytotoxic lignan Podophyllotoxin by cell cultures derived from Linum flavum was investigated. Four cyclodextrins: beta-cyclodextrin, gamma-cyclodextrin, dimethyl-beta-cyclodextrin and hydroxypropyl-beta-cyclodextrin were used to improve the solubility of Podophyllotoxin by complexation. Dimethyl-beta-cyclodextrin met our needs the best and the solubility of Podophyllotoxin could be enhanced from 0.15 to 1.92 mM, using a Podophyllotoxin/cyclodextrin ratio of 1:1. Growth parameters of the cell suspensions were not affected neither by the addition of cyclodextrins alone, nor when complexed Podophyllotoxin was dissolved in the medium. The complexed lignan disappeared rapidly from the culture medium, within 24 h, under all experimental conditions. Almost simultaneously, between 73 and 100% of detectable Podophyllotoxin was bioconverted into Podophyllotoxin-beta-D-glucoside. A maximal bioconversion rate of 0.51 mmol l-1 suspension day-1 was calculated for the L. flavum cells growing in a medium which included the Podophyllotoxin/dimethyl-beta-cyclodextrin complex at a final concentration of 1.35 mM.
Charles L. Cantrell - One of the best experts on this subject based on the ideXlab platform.
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Podophyllotoxin and essential oil profile of juniperus and related species
Industrial Crops and Products, 2013Co-Authors: Charles L. Cantrell, Valtcho D. Zheljazkov, Weste L.a. Osbrink, Amaya Castro, Victor Maddox, Lyle E. Craker, Tess AstatkieAbstract:Podophyllotoxin is currently in high demand as the lead chemical precursor for the anti-cancer drugs etoposide and teniposide. We conducted a two-phase study: (i) screening of Juniperus and other related species and identified Juniperus virginiana as the species with the highest Podophyllotoxin concentration and (ii) established the limits of variations of Podophyllotoxin and essential oil content and composition in J. virginiana in the United States. In the second phase of the study, J. virginiana trees at 49 locations in Mississippi, Alabama, Tennessee, and North Dakota were sampled and analyzed for both Podophyllotoxin and essential oil. Both the essential oil and Podophyllotoxin had similar concentration ranges as percent of dry J. virginiana leaves. Hence the following qualitative grouping with respect to concentration of natural products in the leaves was assigned: very high (>0.3%), high (0.2–0.3%), medium (0.1–0.2%), and low (<0.1%). Based on the above qualitative grouping, the J. virginiana accession were divided into 10 different groups (chemotypes). The J. virginiana accessions also differed in essential oil composition, with wide variation of individual constituents. Based on the essential oil composition, the J. virginiana accessions were divided into the following groups (chemotypes): (1) safrole–limonene–linalool; (2) safrole–β-pinene–limonene–linalool; (3) β-pinene–limonene; (4) limonene; (5) limonene–linalool; (6) limonene–safrole; (7) limonene–safrole–β-pinene; (8) β-pinene–limonene–bornyl acetate; (9) β-pinene–limonene–linalool–bornyl acetate; and (10) myrcene–limonene chemotype. The essential oil of two of the J. virginiana chemotypes showed differential antioxidant activity. J. virginiana leaves, a by-product from the timber industry could be used as a sustainable source for both Podophyllotoxin and essential oil. The availability of various chemotypes offers an opportunity for the development of cultivars for commercial production of Podophyllotoxin and essential oil with specific compositional profile to meet the market requirements.
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Bioprospecting for Podophyllotoxin in the Big Horn Mountains, Wyoming
Industrial Crops and Products, 2013Co-Authors: Valtcho D. Zheljazkov, Charles L. Cantrell, Mateus Augusto Donega, Tess AstatkieAbstract:Abstract The objective of this study was to evaluate variations in Podophyllotoxin concentrations in Juniperus species found in the Big Horn Mountains in Wyoming. It was found that Juniperus species in the Big Horn Mountains included three species; J. communis L. (common juniper), J. horizontalis Moench. (creeping juniper) and J. scopulorum Sarg. (Rocky Mountain juniper). Of these species, none of the 12 accessions of J. communis contained detectable amounts of Podophyllotoxin. All accessions of J. scopulorum but one contained Podophyllotoxin. Podophyllotoxin concentration in J. horizontalis and J. scopulorum did not correlate to the elevation of the selection sites. The concentration of Podophyllotoxin in J. scopulorum ranged from 0 to 0.40%, while the concentration of Podophyllotoxin in J. horizontalis ranged from 0.27 to 0.73%. Overall, J. horizontalis accessions in the Big Horn Mountains showed higher concentration of Podophyllotoxin than the one in J. scopulorum. The range of concentrations in Podophyllotoxin in J. horizontalis and J. scopulorum in the Big Horn Mountains were within the range or (in case of J. horizontalis), much higher than the ones reported previously for J. virginiana. This is the first report on Podophyllotoxin in J. horizontalis. The concentrations of Podophyllotoxin in some accessions of J. horizontalis were twice as high as the ones reported previously for any other junipers. This study demonstrated that Juniperus species in the Big Horn Mountains have a potential to be used as a source for Podophyllotoxin.
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Podophyllotoxin and essential oil profile of Juniperus and related species
Industrial Crops and Products, 2013Co-Authors: Charles L. Cantrell, Valtcho D. Zheljazkov, Weste L.a. Osbrink, Amaya Castro, Victor Maddox, Lyle E. Craker, Tess AstatkieAbstract:Podophyllotoxin is currently in high demand as the lead chemical precursor for the anti-cancer drugs etoposide and teniposide. We conducted a two-phase study: (i) screening of Juniperus and other related species and identified Juniperus virginiana as the species with the highest Podophyllotoxin concentration and (ii) established the limits of variations of Podophyllotoxin and essential oil content and composition in J. virginiana in the United States. In the second phase of the study, J. virginiana trees at 49 locations in Mississippi, Alabama, Tennessee, and North Dakota were sampled and analyzed for both Podophyllotoxin and essential oil. Both the essential oil and Podophyllotoxin had similar concentration ranges as percent of dry J. virginiana leaves. Hence the following qualitative grouping with respect to concentration of natural products in the leaves was assigned: very high (>0.3%), high (0.2–0.3%), medium (0.1–0.2%), and low (
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Podophyllotoxin Concentration in Junipers in the Big Horn Mountains in Wyoming
HortScience, 2012Co-Authors: Valtcho D. Zheljazkov, Charles L. Cantrell, Tess Astatkie, Mateus Augusto Donega, Bonnie HeidelAbstract:Podophyllotoxin is used for the production of the anticancer drugs etoposide, etopophos, and teniposide. Currently, Podophyllotoxin is extracted from the Himalayan mayapple (Podophyllum hexandrum Royle). Some junipers and other species also contain the same natural product and have been explored as a domestic source for this compound. The objective of this study was to screen junipers in the Big Horn Mountains in Wyoming for Podophyllotoxin. Twenty junipers (18 accessions of Juniperus horizontalis Moench. and two accessions of J. scopulorum Sarg.) were sampled in Mar. 2012 and analyzed for Podophyllotoxin. Podophyllotoxin concentration in the samples varied from 0.058% to 0.673% with five accessions having podophylloxin concentration above 0.5%. This study demonstrated wide variation of Podophyllotoxin in J. horizontalis and J. scopulorum in the Big Horn Mountains. Some of the accessions had greater than 0.5% Podophyllotoxin making them a feasible source for Podophyllotoxin extraction.
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Variation in Podophyllotoxin concentration in leaves and rhizomes of American mayapple (Podophyllum peltatum L.)
Industrial Crops and Products, 2011Co-Authors: Valtcho D. Zheljazkov, Charles L. Cantrell, Tess AstatkieAbstract:Abstract Podophyllotoxin is a precursor for compounds used in the synthesis of commercially available anticancer drugs and their precursors etoposide, teniposide, and etopophos. Podophyllotoxin is currently obtained from the underground plant parts (roots and rhizomes) of Himalayan mayapple ( Podophyllum emodii Wall.) but is also found in several other species, including American mayapple. There is no information in the literature on Podophyllotoxin concentration in the roots or rhizomes of the American mayapple, and it was not clear if Podophyllotoxin concentration in underground plant parts is correlated with the concentration in aboveground plant parts. The objective of this study was to estimate Podophyllotoxin concentration in the leaves and rhizomes of 28 accessions of American mayapple under natural conditions (wild) and compare this to Podophyllotoxin concentrations of the same accessions in the leaves when cultivated. Podophyllotoxin concentration in the rhizomes was positively correlated to soil organic matter content and to the concentrations of soil-available P and Na. Podophyllotoxin in the leaves was negatively correlated to soil-available Mg concentrations. The concentration of Podophyllotoxin in the leaves varied from undetectable amounts to 2.52%, whereas Podophyllotoxin in rhizomes varied from 0.14% to 0.42%. Most of the accessions had greater than 0.45% Podophyllotoxin concentration in the leaves under both wild and cultivated conditions. There was no significant correlation between the Podophyllotoxin concentrations in rhizomes and leaves; nine accessions had the highest Podophyllotoxin concentration in leaves under natural environment. Another nine accessions had the highest Podophyllotoxin in the leaves under cultivated conditions, and an additional eight accessions had greater Podophyllotoxin concentrations in roots than in leaves irrespective of the environment. The results from this study may contribute toward developing American mayapple into a new cash crop for U.S. farmers.
Ernest Hamel - One of the best experts on this subject based on the ideXlab platform.
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computational and molecular modeling evaluation of the structural basis for tubulin polymerization inhibition by colchicine site agents
Bioorganic & Medicinal Chemistry, 1996Co-Authors: Ernst Ter Haar, Herbert S Rosenkranz, Ernest HamelAbstract:The computer-automated structure evaluation programs MultiCASE and CASE were used to perform a quantitative structure-activity relationship study on tubulin polymerization inhibitors. A learning set of 536 chemicals (202 active, 27 marginal, and 307 inactive), built using IC50 values for inhibition of tubulin polymerization or mitosis from this and previous studies, was used for artificial intelligence self-teaching. The algorithms successfully predicted the activity of agents in the learning set with > 90% accuracy. Seventeen MultiCASE and twelve CASE (mostly included in the MultiCASE set) biophores (substructures significantly correlated with activity) were identified with a probability > 0.95. Here we present the biophores of Podophyllotoxins, colchicinoids, and certain combretastatins, each examined for structure-activity relationships. For the Podophyllotoxins and colchicinoids in the learning set, the correlations between observed and predicted potencies were > 0.85. The algorithms recognized the importance of several known site, electronic, and steric effects in the two classes. A predictive QSAR (R2 = 0.98) was developed for combretastatin A-2 and dihydrocombretastatin analogues. The MultiCASE/CASE analyzes were used in combination with molecular models to study relative orientations of colchicine, Podophyllotoxin, combretastatin A-4, and steganacin at the colchicine site. This resulted in a new hypothesis, consistent with extensive published experimental data, in which the C-ring and part of the B-ring of colchicine overlap with the A- and B-rings of Podophyllotoxin. Consequently, the trimethoxyphenyl rings of colchicine and Podophyllotoxin occupied different regions of space, each pointing out from a hydrophobic ‘core’ occupied by the overlapping biophores. The molecular model of the highly potent combretastatin A-4 could fit into the model binding site in at least three different ways. The developed QSARs were used to identify the potent microtubule stabilizer discodermolide. Its identification, in concert with recently reported findings, suggest potential overlap in the colchicine and paclitaxel binding sites on tubulin.
