Abstract
The present study aims at determining the structure-activity relationships (SAR's) ruling the biological function of MGBG (methylglyoxal bis(guanylhydrazone)), a competitive inhibitor of S-adenosyl-L-methionine decarboxylase displaying anticancer activity, involved in the biosynthesis of the naturally occurring polyamines spermidine and spermine. In order to properly understand its biochemical activity, MGBG's structural preferences at physiological conditions were ascertained, by quantum mechanical (DFT) calculations.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenosylmethionine Decarboxylase / antagonists & inhibitors
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Animals
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Antineoplastic Agents / chemistry*
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Antineoplastic Agents / metabolism
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Antineoplastic Agents / pharmacology*
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Binding Sites
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Calcium / antagonists & inhibitors
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Calcium / pharmacology
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Cell Membrane Permeability / drug effects
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Cell Membrane Permeability / physiology
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Computer Simulation
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Dose-Response Relationship, Drug
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / metabolism
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Enzyme Inhibitors / pharmacology
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Hepatocytes / chemistry
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Hepatocytes / drug effects
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Hepatocytes / metabolism
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Hydrogen-Ion Concentration
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Male
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Mitochondria, Liver / drug effects
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Mitochondria, Liver / physiology
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Mitoguazone / chemistry*
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Mitoguazone / metabolism
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Mitoguazone / pharmacology*
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Models, Biological*
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Models, Molecular
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Quantum Theory
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Rats
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Rats, Wistar
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Spermidine / antagonists & inhibitors
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Spermidine / pharmacology
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Spermine / antagonists & inhibitors
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Spermine / pharmacology
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Structure-Activity Relationship
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Time Factors
Substances
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Antineoplastic Agents
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Enzyme Inhibitors
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Spermine
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Adenosylmethionine Decarboxylase
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Mitoguazone
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Calcium
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Spermidine