The Experts below are selected from a list of 33 Experts worldwide ranked by ideXlab platform
Nunez I De Castro - One of the best experts on this subject based on the ideXlab platform.
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polyamine contents of human Breast cancer cells treated with the cytotoxic agents chlorpheniramine and <B>DehydrodidemninB> B
Cancer Letters, 1997Co-Authors: P M Gomezfabre, Nunez I De Castro, E De Pedro, Miguel Angel Medina, Javier MarquezAbstract:The cytotoxic agents chlorpheniramine and <B>DehydrodidemninB> B decreased the cell growth of estrogen receptor-negative human Breast cancer cells MDA-MB231 and estrogen receptor-positive MCF-7, after 48 h treatment. Both agents reduced ornithine decarBoxylase activity, But polyamine levels were increased in MDA-MB231 cells treated with <B>DehydrodidemninB> B. MCF-7 cells when treated with <B>DehydrodidemninB> B showed significant increases in spermidine and spermine contents. The results suggest that Besides other effects, the cytotoxicity of DDB could Be explained in part By the over-accumulation of spermidine and spermine.
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effect of <B>DehydrodidemninB> B on human colon carcinoma cell lines
Anticancer Research, 1997Co-Authors: Carolina Lobo, S G Garciapozo, Nunez I De Castro, Francisco J AlonsoAbstract:Didemnins are cytotoxic agents Belonging to a depsipeptide family isolated from marine tunicates. In the present study, a new memBer, <B>DehydrodidemninB> B (DDB), isolated from the mediterranean tunicate Aplidium alBicans, was used. The effect of the drug on human colon cultured cell lines was tested using multiple approaches: proliferation studies, long term survival after three hours of exposure to DDB By means of a clonogenic assay and the decrease of the protooncogen, ornithine decarBoxylase, activity. A <B>DehydrodidemninB> B concentration of 10(-8) M completely inhiBited cell growth. The IC50 oBtained using the MTT proliferation test, indicated that the most proliferative cell line (CT-2) was the most sensitive to the drug. Using a clonogenic assay a clear dose-response was oBtained for the three cell lines used; HT-29 cell line showed the minimum survival after 3 hours of <B>DehydrodidemninB> B treatment. A dose-dependent decrease in ornithine decarBoxylase activity was also oBserved in three cell lines assayed. The data presented indicate that the <B>DehydrodidemninB> B is a potent cytotoxic agent on rapidly dividing human colon cancer cells.
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antiproliferative effect of <B>DehydrodidemninB> B ddB a depsipeptide isolated from mediterranean tunicates
Cancer Letters, 1996Co-Authors: Jose Luis Urdiales, Nunez I De Castro, Pilar Morata, Francisca SanchezjimenezAbstract:The Biological effects of <B>DehydrodidemninB> B(DDB), a novel depsipeptide isolated from Aplidium alBicans, were studied on Ehrlich carcinoma growing in vivo and in primary cultures, and compared with those reported for Didemnin B (DB). Daily administration of DB or DDB (2.5 micrograms/mouse) almost duplicated the animal life-span and total numBer of tumour cells decreased By 70-90%. Results suggest a major effect of DDB when administered in the lag phase of growth. DDB Behaved as a very potent inhiBitor of protein synthesis; consequently, ornithine decarBoxylase activity (ODC, EC 4.1.1.17) is drastically reduced By DDB-treatment.
Francisca Sanchezjimenez - One of the best experts on this subject based on the ideXlab platform.
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antiproliferative effect of <B>DehydrodidemninB> B ddB a depsipeptide isolated from mediterranean tunicates
Cancer Letters, 1996Co-Authors: Jose Luis Urdiales, Nunez I De Castro, Pilar Morata, Francisca SanchezjimenezAbstract:The Biological effects of <B>DehydrodidemninB> B(DDB), a novel depsipeptide isolated from Aplidium alBicans, were studied on Ehrlich carcinoma growing in vivo and in primary cultures, and compared with those reported for Didemnin B (DB). Daily administration of DB or DDB (2.5 micrograms/mouse) almost duplicated the animal life-span and total numBer of tumour cells decreased By 70-90%. Results suggest a major effect of DDB when administered in the lag phase of growth. DDB Behaved as a very potent inhiBitor of protein synthesis; consequently, ornithine decarBoxylase activity (ODC, EC 4.1.1.17) is drastically reduced By DDB-treatment.
Javier Marquez - One of the best experts on this subject based on the ideXlab platform.
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polyamine contents of human Breast cancer cells treated with the cytotoxic agents chlorpheniramine and <B>DehydrodidemninB> B
Cancer Letters, 1997Co-Authors: P M Gomezfabre, Nunez I De Castro, E De Pedro, Miguel Angel Medina, Javier MarquezAbstract:The cytotoxic agents chlorpheniramine and <B>DehydrodidemninB> B decreased the cell growth of estrogen receptor-negative human Breast cancer cells MDA-MB231 and estrogen receptor-positive MCF-7, after 48 h treatment. Both agents reduced ornithine decarBoxylase activity, But polyamine levels were increased in MDA-MB231 cells treated with <B>DehydrodidemninB> B. MCF-7 cells when treated with <B>DehydrodidemninB> B showed significant increases in spermidine and spermine contents. The results suggest that Besides other effects, the cytotoxicity of DDB could Be explained in part By the over-accumulation of spermidine and spermine.
Ernest Giralt - One of the best experts on this subject based on the ideXlab platform.
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conformational analysis of <B>DehydrodidemninB> B aplidine By nmr spectroscopy and molecular mechanics dynamics calculations
Journal of Organic Chemistry, 2001Co-Authors: Francisco Cardenas, Michael Thormann, Miguel Feliz, Josepmaria Caba, Paul Lloydwilliams, Ernest GiraltAbstract:<B>DehydrodidemninB> B (DDB or aplidine), a potent antitumoral natural product currently in phase II clinical trials, exists as an approximately 1:1 mixture of two slowly interconverting conformations. These are sufficiently long-lived so as to allow their resolution By HPLC. NMR spectroscopy shows that this phenomenon is a consequence of restricted rotation aBout the Pyr-Pro8 terminal amide Bond of the molecule's side chain. The same technique also indicates that the overall three-dimensional structures of Both the cis and trans isomers of DDB are similar despite the conformational change. Molecular dynamics simulations with different implicit and explicit solvent models show that the ensemBles of three-dimensional structures produced are indeed similar for Both the cis and trans isomers. These studies also show that hydrogen Bonding patterns in Both isomers are alike and that each one is staBilized By a hydrogen Bond Between the pyruvyl unit at the terminus of the molecule's side chain and the Thr6 residue s...
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total synthesis of <B>DehydrodidemninB> B use of uronium and phosphonium salt coupling reagents in peptide synthesis in solution
ChemInform, 1997Co-Authors: Gemma Jou, Paul Lloydwilliams, Isabel Gonzalez, Fernando Albericio, Ernest GiraltAbstract:New total syntheses of didemnin A and of <B>DehydrodidemninB> B are descriBed. The latter didemnin has the highest antiproliferative activity of all memBers of this family of macrocyclic depsipeptides. It was produced on coupling the side chain Pyr-Pro-OH to didemnin A, which was itself synthesized By two novel routes. One of these was Based on the elaBoration of a linear heptadepsipeptide incorporating the first amino acid of the didemnin side chain, (R)-N(Me)-Leu. Deprotection of the amino and carBoxyl terminii of this linear precursor followed By macrocyclization gave a protected derivative of didemnin A. The second route involved synthesis of the Boc-protected didemnin macrocycle from a linear hexadepsipeptide lacking (R)-N(Me)-Leu. Removal of the Boc group from the macrocycle followed By its coupling with Boc-(R)-N(Me)-Leu-OH then gave Boc-didemnin A. The overall yield was much higher for the second strategy (27% compared to 4% for the first synthesis), But Both allowed synthetic didemnin A, identical wit...
Jose Luis Urdiales - One of the best experts on this subject based on the ideXlab platform.
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antiproliferative effect of <B>DehydrodidemninB> B ddB a depsipeptide isolated from mediterranean tunicates
Cancer Letters, 1996Co-Authors: Jose Luis Urdiales, Nunez I De Castro, Pilar Morata, Francisca SanchezjimenezAbstract:The Biological effects of <B>DehydrodidemninB> B(DDB), a novel depsipeptide isolated from Aplidium alBicans, were studied on Ehrlich carcinoma growing in vivo and in primary cultures, and compared with those reported for Didemnin B (DB). Daily administration of DB or DDB (2.5 micrograms/mouse) almost duplicated the animal life-span and total numBer of tumour cells decreased By 70-90%. Results suggest a major effect of DDB when administered in the lag phase of growth. DDB Behaved as a very potent inhiBitor of protein synthesis; consequently, ornithine decarBoxylase activity (ODC, EC 4.1.1.17) is drastically reduced By DDB-treatment.