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 Apr:157:108239. doi: 10.1016/j.bioorg.2025.108239. Epub 2025 Feb 4.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Calcitriol / analogs & derivatives
  • Cell Proliferation* / drug effects
  • Crystallography, X-Ray
  • Dose-Response Relationship, Drug
  • Drug Design*
  • Humans
  • MCF-7 Cells
  • Models, Molecular
  • Molecular Structure
  • Receptors, Calcitriol* / metabolism
  • Structure-Activity Relationship

Substances

  • Receptors, Calcitriol
  • 1,25-dihydroxy-21-(3-hydroxy-3-methylbutyl)vitamin D(3)
  • Antineoplastic Agents
  • Calcitriol