Abstract
(±)-MRJF22 [(±)-2], a novel prodrug of haloperidol metabolite II (sigma-1 receptor antagonist/sigma-2 receptor agonist ligand) obtained by conjugation to valproic acid (histone deacetylase inhibitor) via an ester bond, exhibits antiangiogenic activity, being able to reduce human retinal endothelial cell (HREC) viability in a comparable manner to bevacizumab. Moreover, (±)-2 was able to significantly reduce viable cells count, endothelial cell migration, and tube formation in vascular endothelial growth factor A (VEGF-A) stimulated HREC cultures.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Angiogenesis Inhibitors / chemical synthesis
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Angiogenesis Inhibitors / chemistry
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Angiogenesis Inhibitors / pharmacology*
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Cell Survival / drug effects
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Dose-Response Relationship, Drug
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Endothelial Cells / cytology
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Endothelial Cells / drug effects*
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Haloperidol / chemical synthesis
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Haloperidol / chemistry
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Haloperidol / pharmacology*
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Humans
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Microvessels / drug effects*
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Molecular Structure
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Neovascularization, Physiologic / drug effects*
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Retina / cytology*
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Structure-Activity Relationship
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Valproic Acid / chemical synthesis
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Valproic Acid / chemistry
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Valproic Acid / pharmacology*
Substances
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Angiogenesis Inhibitors
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Valproic Acid
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Haloperidol