2. Academic Validation
  3. Novel Sigma Receptor Ligand-Nitric Oxide Photodonors: Molecular Hybrids for Double-Targeted Antiproliferative Effect

Novel Sigma Receptor Ligand-Nitric Oxide Photodonors: Molecular Hybrids for Double-Targeted Antiproliferative Effect

  • J Med Chem. 2017 Dec 14;60(23):9531-9544. doi: 10.1021/acs.jmedchem.7b00791.
Emanuele Amata 1,  Maria Dichiara 1,  Emanuela Arena 1,  Valeria Pittalà 1,  Venerando Pistarà 2,  Venera Cardile 3,  Adriana Carol Eleonora Graziano 3,  Aurore Fraix 4,  Agostino Marrazzo 1,  Salvatore Sortino 4,  Orazio Prezzavento 1
Affiliations

Affiliations

  • 1 Department of Drug Sciences, Medicinal Chemistry Section, University of Catania , Viale A. Doria 6, 95125 Catania, Italy.
  • 2 Department of Drug Sciences, Laboratory of Organic Chemistry, University of Catania , Viale A. Doria 6, 95125 Catania, Italy.
  • 3 Department of Biomedical and Biotechnological Sciences, Physiology Section, University of Catania , Via Santa Sofia 97, 95123 Catania, Italy.
  • 4 Department of Drug Sciences, Laboratory of Photochemistry, University of Catania , Viale A. Doria 6, 95125 Catania, Italy.
PMID: 29172528 DOI: 10.1021/acs.jmedchem.7b00791
Abstract

This contribution reports the synthesis and evaluation of novel hybrid compounds that conjugate a sigma (σ) receptor pharmacophore and a nitric oxide (NO) photodonor. All compounds preserve their capability to generate NO under visible light and possess overall σ receptor nanomolar affinity, with one of them (8b) exhibiting remarkable σ2 receptor selectivity. Compounds 8b, 11a, and 11b were tested on tumorigenic MCF-7 and A2058 cells expressing high levels of σ2 and σ1 receptor, respectively. Considerable loss of cell viability was detected under light excitation, while negligible effects in the dark were detected. Moreover, they did not show any significant cytotoxicity in the dark or under irradiation on nontumorigenic NCTC-2544 keratinocytes. NO-induced reduction of cellular viability was demonstrated by in-cell NO detection and total nitrite estimation. For the first time, a combination of σ receptor moieties and a NO photodonor is reported, providing distinctive ligands potentially useful for Cancer management.

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