Synthesis and evaluation of haloperidol metabolite II prodrugs as anticancer agents.

Abstract

The use of haloperidol metabolite II (HP-metabolite II) prodrugs is an emerging strategy in the treatment of cancer. HP-metabolite II exhibits antiproliferative properties at micromolar concentrations inducing apoptosis in different types of cancer. Thus, the application of the prodrug approach appears as a useful method leading to much more desirable pharmacokinetic and pharmacodynamic properties. Some studies have shown that the esterification of the hydroxyl group of HP-metabolite II with 4-phenylbutiric acid (4-PBA) or valproic acid enhances the anticancer therapeutic potency. The current progresses in the design, synthesis and evaluation of anticancer activity of HP metabolite II prodrugs will be discussed in this review.

• Authors: Maria Dichiara, Emanuele Amata, Antonio Rescifina, Orazio Prezzavento, Giuseppe Floresta, Carmela Parenti, Valeria Pittalà, Agostino Marrazzo
• Journal: Future medicinal chemistry (Future Med Chem) Vol. 9 Issue 15 Pg. 1749-1764 (10 2017) ISSN: 1756-8927 [Electronic] England
• PMID: 28869398 (Publication Type: Journal Article, Review)

Chemical References

• Antineoplastic Agents
• Histone Deacetylase Inhibitors
• Phenylbutyrates
• Prodrugs
• Receptors, sigma
• Valproic Acid
• Haloperidol

Topics

• Antineoplastic Agents (chemical synthesis, pharmacology)
• Cell Survival (drug effects)
• Haloperidol (chemistry, metabolism, pharmacology)
• Histone Deacetylase Inhibitors (chemical synthesis, chemistry, pharmacology)
• Humans
• Phenylbutyrates (chemistry, pharmacology)
• Prodrugs (chemical synthesis, pharmacology)
• Receptors, sigma (antagonists & inhibitors, metabolism)
• Signal Transduction (drug effects)
• Valproic Acid (chemistry, pharmacology)