2. Academic Validation
  3. New UB006 Derivatives With Higher Solubility and Cytotoxic Activity in Ovarian Cancer Cells

New UB006 Derivatives With Higher Solubility and Cytotoxic Activity in Ovarian Cancer Cells

  • Pharmaceuticals (Basel). 2025 Jan 31;18(2):194. doi: 10.3390/ph18020194.
Marc Reina 1 2 3,  Xavier Ariza 2 3 4,  Dolors Serra 1 3 4,  Jordi Garcia 2 3 4,  Laura Herrero 1 3 4
Affiliations

Affiliations

  • 1 Department of Biochemistry and Physiology, School of Pharmacy and Food Sciences, Universitat de Barcelona, E-08028 Barcelona, Spain.
  • 2 Department of Inorganic and Organic Chemistry, School of Chemistry, Universitat de Barcelona, E-08028 Barcelona, Spain.
  • 3 Institut de Biomedicina de la Universitat de Barcelona (IBUB), Universitat de Barcelona, E-08028 Barcelona, Spain.
  • 4 Centro de Investigación Biomédica en Red (CIBER) de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, E-28029 Madrid, Spain.
PMID: 40006009 DOI: 10.3390/ph18020194
Abstract

Background/objectives: The compound (±)-UB006 ((4SR,5SR)-4-(hydroxymethyl)-3-methylene-5-octyldihydrofuran-2(3H)-one) is a promising anti-cancer molecule. The enantiomer (-)-UB006 displays a potent cytotoxic effect in several tumor cell lines, particularly the ovarian Cancer OVCAR-3 cell line, with a 40-fold increase in potency compared with the fatty acid synthase (FAS) inhibitor C75. Furthermore, in vivo, (-)-UB006 reduced the tumor burden in neuroblastoma xenografts. This effect was attributed to FAS inhibition and upregulation of apoptotic markers. However, CoA adducts of UB006 presented low solubility.

Methods: We synthesized several (±)-UB006 derivatives by elongating the carbon chain of the primary alcohol and/or by adding hydroxyl groups with the aim of finding more potent and soluble anti-cancer compounds.

Results: Our results showed a decrease in cytotoxicity when the carbon chain was elongated by more than two carbons. However, ethyl or propyl polyhydroxylated four-branched compounds showed an increased or maintained potency and solubility. The most promising compound was (±)-UB035 (IC50: 2.1 ± 0.2 µM), with a 2.5-fold increase in cytotoxicity in the OVCAR-3 cell line and a >4-fold increase in solubility (>2 mM) compared with (±)-UB006.

Keywords

UB006; cancer; cytotoxicity; fatty acid synthase.

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