Synthesis and biological evaluation of radioiodinated 3-phenylcoumarin derivatives targeting myelin in multiple sclerosis

Bioorg Med Chem Lett. 2020 Dec 15;30(24):127562. doi: 10.1016/j.bmcl.2020.127562. Epub 2020 Sep 22.

Abstract

Myelin is a lipid multilayer involved in the rate of nerve transmission, and its loss is a pathological feature of multiple sclerosis in brains. Since in vivo imaging of myelin may be useful for drug development, early diagnosis, and monitoring the disease stage, we designed, synthesized, and evaluated eight novel radioiodinated 3-phenylcoumarin derivatives as imaging probes targeting myelin. In the biodistribution study using normal mice, all compounds displayed sufficient brain uptake, ranging from 2.5 to 5.0% ID/g, at 2 min postinjection. On ex vivo autoradiography, [125I]18 and [125I]21, which have a dimethylamino group, showed high binding affinity for myelin in the normal mouse brain. In addition, the radioactivity accumulation of [125I]21 in the white matter of the spinal cord in the experimental autoimmune encephalomyelitis mice was lower than that in naive mice. These results suggest that [123I]21 shows potential as a single photon emission computed tomography probe targeting myelin.

Keywords: Multiple sclerosis; Myelin; Radioiodinated phenylcoumarin; Single photon emission computed tomography.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoradiography
  • Brain / metabolism
  • Brain / pathology
  • Coumarins / chemical synthesis
  • Coumarins / chemistry*
  • Coumarins / pharmacokinetics
  • Encephalomyelitis, Autoimmune, Experimental / diagnosis*
  • Encephalomyelitis, Autoimmune, Experimental / metabolism
  • Iodine Radioisotopes / chemistry*
  • Iodine Radioisotopes / pharmacokinetics
  • Mice
  • Multiple Sclerosis / diagnosis*
  • Multiple Sclerosis / metabolism
  • Myelin Sheath / metabolism
  • Myelin Sheath / pathology*
  • Radiopharmaceuticals / chemical synthesis
  • Radiopharmaceuticals / chemistry
  • Radiopharmaceuticals / pharmacokinetics
  • Tissue Distribution

Substances

  • Coumarins
  • Iodine Radioisotopes
  • Radiopharmaceuticals
  • Iodine-123
  • coumarin
  • Iodine-125