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Synthesis of Vorinostat and cholesterol conjugate to enhance the cancer cell uptake selectivity.

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.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Idippily ND,Gan C,Orefice P,Peterson J,Su B

doi

10.1016/j.bmcl.2017.01.025

subject

Has Abstract

pub_date

2017-02-15 00:00:00

pages

816-820

issue

4

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(17)30036-7

journal_volume

27

pub_type

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