ORCID ID

Bioorganic and Medicinal Chemistry Letters

Document Type

Article

Publication Date

2017

Publication Title

Bioorganic & Medicinal Chemistry Letters

Abstract

Histone deacetylase (HDAC) inhibitors modulate various cellular functions including proliferation, differentiation, and apoptosis. Vorinostat (SuberAniloHydroxamic Acid, SAHA) is the first HDAC inhibitor approved by FDA for cancer treatment. However, SAHA distributes in cancer tissue and normal tissue in similar levels. It will be ideal to selectively deliver SAHA into cancer cells. Rapidly growing cancer cells have a great need of cholesterol. Low-density lipoprotein (LDL) is the major cholesterol carrier in plasma and its uptake is mediated by LDL-receptor (LDL-R), a glycoprotein overexpressed on the surface of cancer cells. Herein, we designed and synthesized a SAHA cholesterol conjugate, and further formed the conjugate containing particles with LDL as the carrier. The diameters of the particles were determined. The inhibitory activity of the particles carrying the conjugate was determined with cancer cell proliferation assay, and the hydrolysis of the conjugate by the enzymes in cancer cells was confirmed with LC–MS/MS.

Comments

This work was supported by Center for Gene Regulation in Health and Disease (GRHD) of Cleveland State University and Ohio Department of Development (ODOD) and Cleveland State University summer undergraduate research program.

DOI

10.1016/j.bmcl.2017.01.025

Version

Postprint

Volume

27

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