2. Academic Validation
  3. Synthesis of Vorinostat and cholesterol conjugate to enhance the cancer cell uptake selectivity

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

  • Bioorg Med Chem Lett. 2017 Feb 15;27(4):816-820. doi: 10.1016/j.bmcl.2017.01.025.
Nethrie D Idippily 1,  Chunfang Gan 2,  Paul Orefice 1,  Jane Peterson 1,  Bin Su 3
Affiliations

Affiliations

  • 1 Department of Chemistry, Center for Gene Regulation in Health and Disease, College of Sciences and Health Professions, Cleveland State University, 2121 Euclid Ave., Cleveland, OH 44115, USA.
  • 2 College of Chemistry and Life Science, Key Laboratory of Beibu Gulf Environment Change and Resources Utilization, Guangxi Teachers Education University, Nanning 530001, China.
  • 3 Department of Chemistry, Center for Gene Regulation in Health and Disease, College of Sciences and Health Professions, Cleveland State University, 2121 Euclid Ave., Cleveland, OH 44115, USA. Electronic address: b.su@csuohio.edu.
PMID: 28108250 DOI: 10.1016/j.bmcl.2017.01.025
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.

Keywords

Cancer; Cholesterol; LDL-receptor; SAHA.

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