Design, synthesis and biological evaluation of a novel non-Gemini analog of UVB1 and crystal structure of its complex with the vitamin D receptor
- Bioorg Chem. 2025 Feb 4:157:108239. doi: 10.1016/j.bioorg.2025.108239.
Affiliations
- 1. Departamento de Química Orgánica and Instituto de Investigación Sanitaria Galicia Sur (IISGS), Campus Lagoas Marcosende, Universidad de Vigo 36310 Vigo, Spain.
- 2. Institute of Genetics and Molecular and Cellular Biology (IGBMC), Illkirch 67400 France; CNRS UMR 7104, Illkirch 67400 France; Inserm U1258, Illkirch 67400 France; University of Strasbourg, Illkirch 67400 France.
- 3. Clinical and Experimental Endocrinology, Department of Chronic Diseases and Metabolism, KU Leuven 3000 Leuven, Belgium.
- 4. Institute of Genetics and Molecular and Cellular Biology (IGBMC), Illkirch 67400 France; CNRS UMR 7104, Illkirch 67400 France; Inserm U1258, Illkirch 67400 France; University of Strasbourg, Illkirch 67400 France. Electronic address: [email protected].
- 5. Departamento de Química Orgánica and Instituto de Investigación Sanitaria Galicia Sur (IISGS), Campus Lagoas Marcosende, Universidad de Vigo 36310 Vigo, Spain. Electronic address: [email protected].
- 6. Departamento de Química Orgánica and Instituto de Investigación Sanitaria Galicia Sur (IISGS), Campus Lagoas Marcosende, Universidad de Vigo 36310 Vigo, Spain. Electronic address: [email protected].
PMID: 39938446
DOI: 10.1016/j.bioorg.2025.108239
Abstract
We synthesized UG-650, a novel non-Gemini analog of UVB1 that combines structural features of UVB1 and MC 1288. The evaluation of the bioactivities indicates that UG-650 dose-dependently inhibited MCF-7 cell proliferation. In comparison to calcitriol, slightly lower concentrations of UG-650 were needed to achieve equivalent levels of proliferation inhibition. Structural analysis revealed that the analog forms additional interactions stabilizing VDR active form.
Keywords
Antiproliferative agents; Calcitriol; Cancer; Gemini; Hypercalcemia.