2. Academic Validation
  3. Design, synthesis and antiproliferative activity of raloxifene/histone deacetylase inhibitor hybrids in breast cancer

Design, synthesis and antiproliferative activity of raloxifene/histone deacetylase inhibitor hybrids in breast cancer

  • Eur J Med Chem. 2024 Aug 5:274:116533. doi: 10.1016/j.ejmech.2024.116533.
Yufei Wang 1,  Madline Sauvage 2,  Marine Diennet 2,  Sandra Weber 2,  Sylvie Mader 2,  James L Gleason 3
Affiliations

Affiliations

  • 1 Department of Chemistry, McGill University, 801 Sherbrooke St. W., Montreal, QC, H3A 0B8, Canada.
  • 2 Institute for Research in Immunology and Cancer, Pavillon Marcelle-Coutu, Université de Montréal, 2950 Chemin de Polytechnique, Montréal, QC, H3T 1J4, Canada.
  • 3 Department of Chemistry, McGill University, 801 Sherbrooke St. W., Montreal, QC, H3A 0B8, Canada. Electronic address: jim.gleason@mcgill.ca.
PMID: 38838548 DOI: 10.1016/j.ejmech.2024.116533
Abstract

Antiestrogen/histone deacetylase inhibitor (HDACi) hybrids were designed by merging structures of raloxifene with suberoylanilide hydroxamic acid, incorporating the HDACi unit into the phenolic ring of the antiestrogen. These hybrids were synthesized with a range of HDACi chain lengths and assessed for bifunctionality. Four hybrids, 21 (YW471), 22 (YW490), 27(YW486), and 28 (YW487) showed good potency both as antiestrogens in a BRET assay and in a fluorometric HDACi assay. The antiproliferative activity of the hybrids was demonstrated in both ER+ MCF7 and ER- MDA-MB-231 breast Cancer cell lines.

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