Synthesis and evaluation of haloperidol metabolite II prodrugs as anticancer agents. (October 2017)

• Record Type: Journal Article
• Authors: Dichiara, Maria; Amata, Emanuele; Rescifina, Antonio; Prezzavento, Orazio; Floresta, Giuseppe; Parenti, Carmela; Pittalà, Valeria; Marrazzo, Agostino
• Is Part Of: Future medicinal chemistry. Volume 9:Number 15(2017)
• Page Start: 1749
• Page End: 1764
• Publication Date: 2017-10
• Subjects: antiangiogenesis -- HDACi -- sigma receptor; Pharmaceutical chemistry -- Periodicals; 615.19005
• DOI: 10.4155/fmc-2017-0064
• Languages: English
• ISSNs: 1756-8919

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.