Broad assessment of bioactivity of a collection of spiroindane pyrrolidines through "cell painting"

Bioorg Med Chem. 2020 Jul 1;28(13):115547. doi: 10.1016/j.bmc.2020.115547. Epub 2020 May 19.

Abstract

A collection of small molecules has been synthesized by composing photo-cycloaddition, C-H functionalization, and N-capping strategies. Multidimensional biological fingerprints of molecules comprising this collection have been recorded as changes in cell and organelle morphology. This untargeted, phenotypic approach allowed for a broad assessment of biological activity to be determined. Reproducibility and the magnitude of measured fingerprints revealed activity of several treatments. Reactive functional groups, such as imines, dominated the observed activity. Two non-reactive candidate compounds with distinct bioactivity fingerprints were identified, as well.

Keywords: Biological activity; Complexity; Fingerprints; Photochemistry.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amines / chemistry
  • Cell Line
  • Cyclization
  • Cycloaddition Reaction
  • Humans
  • Imines / chemistry
  • Optical Imaging
  • Organelles / metabolism
  • Organelles / ultrastructure
  • Photochemical Processes
  • Pyrrolidines / chemical synthesis*
  • Pyrrolidines / metabolism*
  • Reproducibility of Results
  • Stereoisomerism

Substances

  • Amines
  • Imines
  • Pyrrolidines