The Experts below are selected from a list of 102 Experts worldwide ranked by ideXlab platform
Karin Scarpinato - One of the best experts on this subject based on the ideXlab platform.
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Targeted Approach to Overcoming Treatment Resistance in Advanced Prostate Cancer
2015Co-Authors: Karin ScarpinatoAbstract:Abstract : The purpose of this project is to determine if Rescinnamine is effective against prostate cancer and treatment resistance. We determined that Rescinnamine is less effective against prostate cancer than against other cancer types, making it less ideal to follow. In addition, the hypotensive activity of Rescinnamine was dose-inhibitive in animal studies. We therefore pursued a combination of computational modeling, chemical synthesis and in vitro testing to identify analogs with higher efficacy and less toxicity. Initial results identified a small number of compounds, some of them entirely novel, that should be followed up on in subsequent studies.
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improving Rescinnamine as an inducer of msh2 dependent apoptosis in cancer treatment
Molecular Cancer Biology, 2013Co-Authors: Karin Scarpinato, Aksana Vasilyeva, Elshimaa M N Abdelhafez, Andrew Diamanduros, Lacramioara Negureanu, J H Bean, K Zielke, B Crowe, Yan Lu, Jill E ClodfelterAbstract:We, and others have previously shown that mismatch repair proteins, in addition to their repair function, have the ability to contribute to cell death initiation. In response to some drugs, this cell death activity is independent of the repair function of the proteins. Rescinnamine, a derivative of the indole alkaloid reserpine, a drug used to treat hypertension several decades ago, was shown to target the cell death-initiating activity of mismatch repair proteins. When used in animals, the hypotensive action of this drug prevents applying appropriate concentrations for statistically significant tumor reduction. Here we used a combination of computational modeling, chemical synthesis and cell assays to determine how Rescinnamine can be modified and what effect these modifications have on cell survival. Results inform further computational modeling to suggest new lead molecules to move toward further testing.
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computational and synthetic studies towards improving Rescinnamine as an inducer of msh2 dependent apoptosis in cancer treatment
Molecular cancer biology, 2013Co-Authors: Elshimaa M N Abdelhafez, Jill E Clodfelter, Aksana Vasilyeva, Andrew Diamanduros, Lacramioara Negureanu, J H Bean, K Zielke, B Crowe, Gamal Eldin A A Abuorahma, Karin ScarpinatoAbstract:: We, and others, have previously shown that mismatch repair proteins, in addition to their repair function, contribute to cell death initiation. In response to some drugs, this cell death activity is independent of the repair function of the proteins. Rescinnamine, a derivative of the indole alkaloid reserpine, a drug used to treat hypertension several decades ago, was shown to target the cell death-initiating activity of mismatch repair proteins. When used in animals, the hypotensive action of this drug prevents applying appropriate concentrations for statistically significant tumor reduction. Using a combination of computational modeling, chemical synthesis and cell assays, we determine how Rescinnamine can be structurally modified and what effect these modifications have on cell survival. These results inform further computational modeling to suggest new synthetic lead molecules to move toward further biological testing.
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parameters of reserpine analogs that induce msh2 msh6 dependent cytotoxic response
Journal of Nucleic Acids, 2010Co-Authors: Aksana Vasilyeva, Jill E Clodfelter, Freddie R. Salsbury, Michael J Gorczynski, Anthony Richard Gerardi, Bruce S King, Karin ScarpinatoAbstract:Mismatch repair proteins modulate the cytotoxicity of several chemotherapeutic agents. We have recently proposed a “death conformation” of the MutS homologous proteins that is distinguishable from their “repair conformation.” This conformation can be induced by a small molecule, reserpine, leading to DNA-independent cell death. We investigated the parameters for a small reserpine-like molecule that are required to interact with MSH2/MSH6 to induce MSH2/MSH6-dependent cytotoxic response. A multidisciplinary approach involving structural modeling, chemical synthesis, and cell biology analyzed reserpine analogs and modifications. We demonstrate that the parameters controlling the induction of MSH2/MSH6-dependent cytotoxicity for reserpine-analogous molecules reside in the specific requirements for methoxy groups, the size of the molecule, and the orientation of molecules within the protein-binding pocket. Reserpine analog Rescinnamine showed improved MSH2-dependent cytotoxicity. These results have important implications for the identification of compounds that require functional MMR proteins to exhibit their full cytotoxicity, which will avoid resistance in MMR-deficient cells.
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Parameters of Reserpine Analogs That Induce MSH2/MSH6-Dependent Cytotoxic Response.
Journal of Nucleic Acids, 2010Co-Authors: Aksana Vasilyeva, Jill E Clodfelter, Freddie R. Salsbury, Michael J Gorczynski, Anthony Richard Gerardi, S. Bruce King, Karin ScarpinatoAbstract:Mismatch repair proteins modulate the cytotoxicity of several chemotherapeutic agents. We have recently proposed a “death conformation” of the MutS homologous proteins that is distinguishable from their “repair conformation.” This conformation can be induced by a small molecule, reserpine, leading to DNA-independent cell death. We investigated the parameters for a small reserpine-like molecule that are required to interact with MSH2/MSH6 to induce MSH2/MSH6-dependent cytotoxic response. A multidisciplinary approach involving structural modeling, chemical synthesis, and cell biology analyzed reserpine analogs and modifications. We demonstrate that the parameters controlling the induction of MSH2/MSH6-dependent cytotoxicity for reserpine-analogous molecules reside in the specific requirements for methoxy groups, the size of the molecule, and the orientation of molecules within the protein-binding pocket. Reserpine analog Rescinnamine showed improved MSH2-dependent cytotoxicity. These results have important implications for the identification of compounds that require functional MMR proteins to exhibit their full cytotoxicity, which will avoid resistance in MMR-deficient cells.
Luciano Saso - One of the best experts on this subject based on the ideXlab platform.
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Inhibition of Candida rugosa lipase by saponins, flavonoids and alkaloids
Journal of Molecular Catalysis B: Enzymatic, 2020Co-Authors: Cristian Ruiz, Serena Falcocchio, Entela Xoxi, Ly Villo, Giovanni Nicolosi, F. I. Javier Pastor, Pilar Diaz, Luciano SasoAbstract:Lipase inhibitors have generated a great interest because they could help in the prevention or the therapy of lipase-related diseases. Therefore, the aim of the work was to evaluate by HPLC, and using Candida rugosa lipase as model, the inhibitory effect of several saponins: beta-aescin, digitonin, glycyrrhizic acid (GA) and Quillaja saponin (QS); flavonoids: 3-hydroxyflavone, 5-hydroxyflavone, (+)-catechin and kaempferol; and alkaloids: aspidospermine, papaverine, physostigmine, pilocarpine, raubasine, Rescinnamine, reserpine and trigonelline. The inhibition produced by most of these compounds is described here for the first time. Saponins appeared very active, being beta-aescin and digitonin the most active compounds (IC50 = 0.8-2.4 x 10(-5) M). The inhibitory activity of flavonoids was lower than that of saponins (except GA), and (+)-catechin and kaempferol were the most active. Alkaloids was the most heterogeneous group assayed, varying from Rescinnamine, with an IC16 similar to that of digitonin, to papaverine and others which showed almost no inhibition. In conclusion, beta-aescin, digitonin, kaempferol or (+)-catechin, strong lipase inhibitors with a low toxicity and present herbal drugs used for lipase-related diseases such as acne or ulcer, are promising candidates for the prevention or the treatment of these diseases. (c) 2006 Elsevier B.V. All rights reserved
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Inhibition of Candida rugosa lipase by saponins, flavonoids and alkaloids
Journal of Molecular Catalysis B-enzymatic, 2006Co-Authors: Cristian Ruiz, Serena Falcocchio, Entela Xoxi, Ly Villo, Giovanni Nicolosi, F. I. Javier Pastor, Pilar Diaz, Luciano SasoAbstract:Abstract Lipase inhibitors have generated a great interest because they could help in the prevention or the therapy of lipase-related diseases. Therefore, the aim of the work was to evaluate by HPLC, and using Candida rugosa lipase as model, the inhibitory effect of several saponins: β-aescin, digitonin, glycyrrhizic acid (GA) and Quillaja saponin (QS); flavonoids: 3-hydroxyflavone, 5-hydroxyflavone, (±)-catechin and kaempferol; and alkaloids: aspidospermine, papaverine, physostigmine, pilocarpine, raubasine, Rescinnamine, reserpine and trigonelline. The inhibition produced by most of these compounds is described here for the first time. Saponins appeared very active, being β-aescin and digitonin the most active compounds (IC 50 = 0.8–2.4 × 10 −5 M). The inhibitory activity of flavonoids was lower than that of saponins (except GA), and (±)-catechin and kaempferol were the most active. Alkaloids was the most heterogeneous group assayed, varying from Rescinnamine, with an IC 16 similar to that of digitonin, to papaverine and others which showed almost no inhibition. In conclusion, β-aescin, digitonin, kaempferol or (±)-catechin, strong lipase inhibitors with a low toxicity and present herbal drugs used for lipase-related diseases such as acne or ulcer, are promising candidates for the prevention or the treatment of these diseases.
Aksana Vasilyeva - One of the best experts on this subject based on the ideXlab platform.
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improving Rescinnamine as an inducer of msh2 dependent apoptosis in cancer treatment
Molecular Cancer Biology, 2013Co-Authors: Karin Scarpinato, Aksana Vasilyeva, Elshimaa M N Abdelhafez, Andrew Diamanduros, Lacramioara Negureanu, J H Bean, K Zielke, B Crowe, Yan Lu, Jill E ClodfelterAbstract:We, and others have previously shown that mismatch repair proteins, in addition to their repair function, have the ability to contribute to cell death initiation. In response to some drugs, this cell death activity is independent of the repair function of the proteins. Rescinnamine, a derivative of the indole alkaloid reserpine, a drug used to treat hypertension several decades ago, was shown to target the cell death-initiating activity of mismatch repair proteins. When used in animals, the hypotensive action of this drug prevents applying appropriate concentrations for statistically significant tumor reduction. Here we used a combination of computational modeling, chemical synthesis and cell assays to determine how Rescinnamine can be modified and what effect these modifications have on cell survival. Results inform further computational modeling to suggest new lead molecules to move toward further testing.
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computational and synthetic studies towards improving Rescinnamine as an inducer of msh2 dependent apoptosis in cancer treatment
Molecular cancer biology, 2013Co-Authors: Elshimaa M N Abdelhafez, Jill E Clodfelter, Aksana Vasilyeva, Andrew Diamanduros, Lacramioara Negureanu, J H Bean, K Zielke, B Crowe, Gamal Eldin A A Abuorahma, Karin ScarpinatoAbstract:: We, and others, have previously shown that mismatch repair proteins, in addition to their repair function, contribute to cell death initiation. In response to some drugs, this cell death activity is independent of the repair function of the proteins. Rescinnamine, a derivative of the indole alkaloid reserpine, a drug used to treat hypertension several decades ago, was shown to target the cell death-initiating activity of mismatch repair proteins. When used in animals, the hypotensive action of this drug prevents applying appropriate concentrations for statistically significant tumor reduction. Using a combination of computational modeling, chemical synthesis and cell assays, we determine how Rescinnamine can be structurally modified and what effect these modifications have on cell survival. These results inform further computational modeling to suggest new synthetic lead molecules to move toward further biological testing.
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parameters of reserpine analogs that induce msh2 msh6 dependent cytotoxic response
Journal of Nucleic Acids, 2010Co-Authors: Aksana Vasilyeva, Jill E Clodfelter, Freddie R. Salsbury, Michael J Gorczynski, Anthony Richard Gerardi, Bruce S King, Karin ScarpinatoAbstract:Mismatch repair proteins modulate the cytotoxicity of several chemotherapeutic agents. We have recently proposed a “death conformation” of the MutS homologous proteins that is distinguishable from their “repair conformation.” This conformation can be induced by a small molecule, reserpine, leading to DNA-independent cell death. We investigated the parameters for a small reserpine-like molecule that are required to interact with MSH2/MSH6 to induce MSH2/MSH6-dependent cytotoxic response. A multidisciplinary approach involving structural modeling, chemical synthesis, and cell biology analyzed reserpine analogs and modifications. We demonstrate that the parameters controlling the induction of MSH2/MSH6-dependent cytotoxicity for reserpine-analogous molecules reside in the specific requirements for methoxy groups, the size of the molecule, and the orientation of molecules within the protein-binding pocket. Reserpine analog Rescinnamine showed improved MSH2-dependent cytotoxicity. These results have important implications for the identification of compounds that require functional MMR proteins to exhibit their full cytotoxicity, which will avoid resistance in MMR-deficient cells.
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Parameters of Reserpine Analogs That Induce MSH2/MSH6-Dependent Cytotoxic Response.
Journal of Nucleic Acids, 2010Co-Authors: Aksana Vasilyeva, Jill E Clodfelter, Freddie R. Salsbury, Michael J Gorczynski, Anthony Richard Gerardi, S. Bruce King, Karin ScarpinatoAbstract:Mismatch repair proteins modulate the cytotoxicity of several chemotherapeutic agents. We have recently proposed a “death conformation” of the MutS homologous proteins that is distinguishable from their “repair conformation.” This conformation can be induced by a small molecule, reserpine, leading to DNA-independent cell death. We investigated the parameters for a small reserpine-like molecule that are required to interact with MSH2/MSH6 to induce MSH2/MSH6-dependent cytotoxic response. A multidisciplinary approach involving structural modeling, chemical synthesis, and cell biology analyzed reserpine analogs and modifications. We demonstrate that the parameters controlling the induction of MSH2/MSH6-dependent cytotoxicity for reserpine-analogous molecules reside in the specific requirements for methoxy groups, the size of the molecule, and the orientation of molecules within the protein-binding pocket. Reserpine analog Rescinnamine showed improved MSH2-dependent cytotoxicity. These results have important implications for the identification of compounds that require functional MMR proteins to exhibit their full cytotoxicity, which will avoid resistance in MMR-deficient cells.
Ugo R Cieri - One of the best experts on this subject based on the ideXlab platform.
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determination of reserpine and Rescinnamine in rauwolfia serpentina powders and tablets collaborative study
Journal of AOAC International, 1998Co-Authors: Ugo R CieriAbstract:: A liquid chromatographic (LC) method for determining reserpine and Rescinnamine in Rauwolfia serpentine powders and tablets, which uses fluorescence detection, was subjected to a collaborative study. The procedure for extraction and purification is a simplified version of that used in the current official method for analysis of these products. LC separations are performed on a normal-phase column. The mobile phase is methanol to which a small volume of an aqueous solution of 1-pentanesulfonic acid sodium salt can be added to achieve desired elution characteristics. Reserpine and Rescinnamine elute at approximately the same time but can be individually quantitated by appropriate settings of the fluorescence detector. Reserpine is determined at an excitation wavelength of 280 nm and an emission wavelength of 360 nm, because Rescinnamine is completely non-fluorescent at these wavelengths. Rescinnamine is determined at an excitation wavelength of 330 nm and an emission wavelength of 435 nm, because reserpine is completely nonfluorescent at these wavelengths. The following materials were used for the study: one sample of United States Pharmacopeia (USP) standard R. serpentine powder, one tablet type labeled as containing 100 mg R. serpentine and 2 tablet types labeled as containing 50 mg R. serpentine. For each of the 4 materials, 2 pairs of blind duplicates were prepared. Three materials were analyzed in duplicate by 8 laboratories. One of the 2 tablets labeled to contain 50 mg R. serpentine was analyzed only by 7 of 8 participating laboratories. Average combined content of reserpine and Rescinnamine was 0.144% for the USP raw material and 0.132, 0.135, and 0.137% for the 3 commercial tablets. Reproducibility relative standard deviation values were 5.72, 5.93, 8.61, and 3.48% and repeatability relative standard deviation values were 2.57, 4.87, 3.19, and 1.99% for the 4 samples. The Associate Referee conducted a study to determine recoveries of reserpine plus Rescinnamine by this method from mixtures simulating sample extracts. Average recovery of 15 determinations was 100.1%, with a relative standard deviation of 1.3%. The LC method for determination of reserpine and Rescinnamine in R. serpentine powders and tablets has been adopted first action by AOAC INTERNATIONAL.
M.vimala Devi - One of the best experts on this subject based on the ideXlab platform.
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Applicability and comparative evaluation of wet granulation and direct compression technology to Rauwolfia serpentina root powder: a technical note.
Aaps Pharmscitech, 2008Co-Authors: Ch. Niranjan Patra, Hemant Kumar Pandit, Satya Prakash Singh, M.vimala DeviAbstract:The dried root of Rauwolfia serpentina, family Apocynaceae is well accepted that the pharmacological effects are due to its alkaloids, especially the reserpine-Rescinnamine group (1,2). It is principally used in treatment of mild hypertension (3), tranquilizer for nervous and mental disorders (4,5). Preliminary investigations of its pharmacological activities justify its use in folk medicine. The dose of R. serpentina powder is 200 mg daily in divided doses for 1–3 weeks (4). Dispensing and consumption of powder formulation is inconvenient to the patients. Hence there is an urgent need for the development of systematic study on methods for standardization of traditional medicine has led to the formulation of R. serpentina powder into tablet dosage form. The measurement of porosity change as a function of compression pressure is widely used in describing the powder compressional behavior. The compressibility of a powder bed could be inferred from the relationship between porosity and applied pressure (6). Due to poor flowability and compaction behavior, R. serpentina powder frequently requires alteration prior to tabletting. Direct compression of powders requires materials exhibiting good flowability, comapactibility and compressibility. These parameters become more critical when the formulation contains large amount of active substances with poor compressional properties. Wet granulation method is selected for production of porous and free-flowing granules, which enables to form tablets with high mechanical strength at low compression pressure. In the present study, attempts were made to develop tablet formulations of R. serpentina powder through alteration of particle size by granulation and direct compression technique after a systematic study on flowability, compactibility and compressibility (7) with an aim to characterize the consolidation behavior.