Abstract |
In a previous work we reported the antiproliferative effects of (±)-MRJF4, a novel haloperidol metabolite II (HP-mII) (a sigma-1 antagonist and sigma-2 agonist) prodrug, obtained through conjugation to 4-phenylbutyric acid (PhBA) [a histone deacetylase inhibitor (HDACi)] via an ester bond. As a continuation of this work, here we report the asymmetric synthesis of compounds (R)-(+)-MRJF4 and (S)-(-)-MRJF4 and the evaluation of their biological activity on rat C6 glioma cells, derived from glioblastoma multiforme (GBM), which is the most common and deadliest central nervous system (CNS) invasive malignancy. Favourable physicochemical properties, high permeability in the parallel artificial membrane permeability assay (PAMPA), good enzymatic and chemical stability, in vivo anticancer activity, associated with the capacity to reduce cell viability and to increase cell death by apoptosis, render compound (R)-(+)-MRJF4 a promising candidate for the development of a useful therapeutic for gliomas therapy.
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Authors | Piera Sozio, Jole Fiorito, Viviana Di Giacomo, Antonio Di Stefano, Lisa Marinelli, Ivana Cacciatore, Amelia Cataldi, Stephanie Pacella, Hasan Turkez, Carmela Parenti, Antonio Rescifina, Agostino Marrazzo |
Journal | European journal of medicinal chemistry
(Eur J Med Chem)
Vol. 90
Pg. 1-9
(Jan 27 2015)
ISSN: 1768-3254 [Electronic] France |
PMID | 25461306
(Publication Type: Journal Article)
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Copyright | Copyright © 2014 Elsevier Masson SAS. All rights reserved. |
Chemical References |
- Antineoplastic Agents
- Prodrugs
- Haloperidol
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Topics |
- Animals
- Antineoplastic Agents
(chemical synthesis, metabolism, pharmacology)
- Apoptosis
(drug effects)
- Cell Survival
(drug effects)
- Dose-Response Relationship, Drug
- Drug Screening Assays, Antitumor
- Glioma
(drug therapy, pathology)
- Haloperidol
(chemical synthesis, metabolism, pharmacology)
- Molecular Structure
- Prodrugs
(chemical synthesis, metabolism, pharmacology)
- Rats
- Structure-Activity Relationship
- Tumor Cells, Cultured
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