Abstract
Structure-activity relationship studies were carried out on a new series of hydrazino-thiosemicarbazide derivatives, which inhibit monoamino oxidase (MAO). Fifty-five compounds were synthesized and tested "in vitro" for their inhibitory effects on rat liver mitochondrial MAO. The most efficient MAO inhibitors were the benzylidene derivatives (sequence: see text] where R is the piperonyl radical and ethyl or isopropyl substituents are in R1 position. Correlation of MAO activity with hydrophobic, electronic and steric properties of tested compounds, evaluated by means of Quantum Mechanical calculations and calorimetric analysis (DSC) suggest that electronic and steric parameters give a better fit than hydrophobicity with the biological activity.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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1,2-Dipalmitoylphosphatidylcholine / metabolism
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Animals
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Binding Sites
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Calorimetry, Differential Scanning
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Chemical Phenomena
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Chemistry
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Electron Transport
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Enzyme Inhibitors / chemical synthesis
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Enzyme Inhibitors / pharmacology
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Hydrazines* / chemical synthesis
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Hydrazines* / pharmacology
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Liposomes / metabolism
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Liver / enzymology
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Molecular Structure
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Monoamine Oxidase / metabolism
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Monoamine Oxidase Inhibitors / chemistry
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Monoamine Oxidase Inhibitors / pharmacology*
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Rats
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Semicarbazides / chemical synthesis
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Semicarbazides / pharmacology*
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Structure-Activity Relationship*
Substances
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Enzyme Inhibitors
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Hydrazines
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Liposomes
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Monoamine Oxidase Inhibitors
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Semicarbazides
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1,2-Dipalmitoylphosphatidylcholine
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Monoamine Oxidase