2. Academic Validation
  3. Hemithioindigo-based histone deacetylase inhibitors induce a light-dependent anticancer effect

Hemithioindigo-based histone deacetylase inhibitors induce a light-dependent anticancer effect

  • Eur J Med Chem. 2024 Sep 6:279:116846. doi: 10.1016/j.ejmech.2024.116846.
Laia Josa-Culleré 1,  Carla Aira Rodríguez 2,  Amadeu Llebaria 3
Affiliations

Affiliations

  • 1 MCS, Laboratory of Medicinal Chemistry & Synthesis, Department of Biological Chemistry, Institute for Advanced Chemistry of Catalonia (IQAC-CSIC), Jordi Girona 18-26, 08034, Barcelona, Spain. Electronic address: laia.josacullere@iqac.csic.es.
  • 2 MCS, Laboratory of Medicinal Chemistry & Synthesis, Department of Biological Chemistry, Institute for Advanced Chemistry of Catalonia (IQAC-CSIC), Jordi Girona 18-26, 08034, Barcelona, Spain.
  • 3 MCS, Laboratory of Medicinal Chemistry & Synthesis, Department of Biological Chemistry, Institute for Advanced Chemistry of Catalonia (IQAC-CSIC), Jordi Girona 18-26, 08034, Barcelona, Spain. Electronic address: amadeu.llebaria@iqac.csic.es.
PMID: 39270453 DOI: 10.1016/j.ejmech.2024.116846
Abstract

Photoswitchable molecules exhibit light-dependent biological activity which allow us to control the therapeutic effect of drugs with high precision. Such molecules could solve some of the limitations of Anticancer drugs by providing a localised effect in the tumour. Histone deacetylase inhibitors (HDACis) constitute a promising drug class for oncology whose application is often limited by a lack of selectivity. Herein, we developed photoswitchable HDACis based on a hemithioindigo scaffold. We established synthetic routes to access them and determined the optimal conditions for isomerisation and their thermal stability. We then optimised their Enzyme activity through three rounds of re-design to identify examples that are up to 6-fold more active under illumination than in the dark. We also confirmed that our best derivative reduces the viability of HeLa cells only under illumination. All in all, we disclose a series of derivatives containing a hemithioindigo moiety, which display a light-dependent effect on both HDAC inhibition and Cancer cell viability.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-162907
    HDAC抑制剂
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