2. Academic Validation
  3. Development of new HO-1 inhibitors by a thorough scaffold-hopping analysis

Development of new HO-1 inhibitors by a thorough scaffold-hopping analysis

  • Bioorg Chem. 2018 Dec;81:334-339. doi: 10.1016/j.bioorg.2018.08.023.
Giuseppe Floresta 1,  Valeria Pittalà 2,  Valeria Sorrenti 2,  Giuseppe Romeo 2,  Loredana Salerno 3,  Antonio Rescifina 2
Affiliations

Affiliations

  • 1 Department of Drug Sciences, University of Catania, V.le A. Doria 6, 95125 Catania, Italy; Department of Chemical Sciences, University of Catania, V.le A. Doria, 95125 Catania, Italy. Electronic address: [email protected].
  • 2 Department of Drug Sciences, University of Catania, V.le A. Doria 6, 95125 Catania, Italy.
  • 3 Department of Drug Sciences, University of Catania, V.le A. Doria 6, 95125 Catania, Italy. Electronic address: [email protected].
PMID: 30189413 DOI: 10.1016/j.bioorg.2018.08.023
Abstract

HO-1 inhibition is considered a valuable Anticancer approach. In fact, up-regulation of HO-1 had been repeatedly reported in many types of human malignancies, and in these clinical cases, poor outcomes are reported. To identify novel HO-1 inhibitors suitable for drug development, a scaffold-hopping strategy calculation was utilized to design novel derivatives. Different parts of the selected molecule were analyzed and the different series of novel compounds were virtually evaluated. The calculation for the linker moiety of the classical HO-1 inhibitors structure led us to compounds 5 and 6. A synthetic pathway for the two molecules was designed and the compounds were synthesized. The biological activity revealed an HO-1 inhibition of 0.9 and 54 μM for molecules 5 and 6 respectively. This study suggested that our scaffold-hopping approach was successful and these results are ongoing for further development.

Keywords

HO-1 imidazole inhibitors; Heme oxygenase-1; Scaffold-hopping.

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