Optically active iodohelicene derivatives exhibit histamine N-methyl transferase inhibitory activity

J Antibiot (Tokyo). 2019 Jun;72(6):476-481. doi: 10.1038/s41429-018-0118-z. Epub 2018 Nov 20.

Abstract

Optically active helicene derivatives inhibit the activity on histamine N-methyl transferase (HNMT). Specifically, methyl (P)-1,12-dimethylbenzo[c]phenanthrene-8-carboxylate with 6-iodo and 5-trifluoromethanesulfonyloxy groups inhibits HNMT activity on the μM order of IC50. Chirality is important, and (M)-isomers exhibits substantially reduced activity. The 6-iodo group is also essential, which suggests the involvement of halogen bonds in protein binding. Substituents on the sulfonate moiety also affect the inhibitory activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Drug Design
  • Histamine N-Methyltransferase / antagonists & inhibitors*
  • Molecular Structure
  • Polycyclic Compounds / chemical synthesis*
  • Polycyclic Compounds / chemistry
  • Structure-Activity Relationship

Substances

  • Polycyclic Compounds
  • helicenes
  • Histamine N-Methyltransferase