Abstract
Aim:
There is little information available on the monoamine oxidase isoform selectivity of N-alkyl harmine analogs, which exhibit a myriad of activities including MAO-A, DYRK1A and cytotoxicity to several select cancer cell lines.
Results:
Compounds 3e and 4c exhibited an IC50 of 0.83 ± 0.03 and 0.43 ± 0.002 μM against MAO-A and an IC50 of 0.26 ± 0.04 and 0.36 ± 0.001 μM against MAO-B, respectively. Molecular docking studies revealed π-π interactions between the synthesized molecules and aromatic amino acid residues. Conclusion & future perspective: The current study delineates the structural requirements for MAO-A selectivity and such information may be helpful in designing selective analogs for kinase, DYRK1A and harmine-based cytotoxics without apparent MAO enzyme inhibition.
Keywords:
1,2,3-triazoles; click chemistry; harmine; monoamine oxidase.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Antineoplastic Agents / chemical synthesis
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology
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Click Chemistry
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Harmine / analogs & derivatives*
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Harmine / chemical synthesis
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Harmine / pharmacology*
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Humans
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Kinetics
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Molecular Docking Simulation
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Monoamine Oxidase / metabolism*
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Monoamine Oxidase Inhibitors / chemical synthesis
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Monoamine Oxidase Inhibitors / chemistry*
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Monoamine Oxidase Inhibitors / pharmacology*
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Neoplasms / drug therapy
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Neoplasms / metabolism
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Protein Isoforms / antagonists & inhibitors
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Protein Isoforms / metabolism
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Structure-Activity Relationship
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Triazoles / chemical synthesis
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Triazoles / chemistry*
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Triazoles / pharmacology*
Substances
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Antineoplastic Agents
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Monoamine Oxidase Inhibitors
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Protein Isoforms
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Triazoles
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Harmine
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Monoamine Oxidase
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monoamine oxidase A, human