Biotransformation into 11α-hydroxyprogesterone glucosides by glucosyltransferase

Steroids. 2019 May:145:32-38. doi: 10.1016/j.steroids.2019.02.008. Epub 2019 Feb 10.

Abstract

Recently, studies on the steroidal hormone activity in the brain have attracted attention, and the influences of the varied glucosides and their artificial derivatives have been discussed; additionally, it has been suggested that glucosides are the synthetic precursors of glucuronide as a label molecule. However, glucosides are formed with 11α-hydroxyprogesterone (1), which is important as a blood pressure regulator, but anti-androgen activity remains unknown. Using UDP-glucosyltransferase, glucoside synthesis was successful in linking β-d-glucopyranose and β-d-laminaribiose to 11α oxygen of 1 at a high conversion ratio, and full assignment structure was analyzed for the two glucosides by high-resolution quadrupole-time flight electrospray ionization-mass spectrometry, 1D (1H and 13C) NMR and 2D (COSY, ROESY, HSQC-DEPT and HMQC) NMR. Furthermore, the bioactivity of 1 and two 11α-hydroxyprogesterone glucosides [11α-(β-d-glucopyranosyl)oxyprogesterone, 2, and 11α-(β-d-laminaribiosyl)oxyprogesterone, 3] was tested in vitro. On rotenone-induced PC12 cells, the two 11α-hydroxyprogesterone glucosides (2 and 3) showed superior neuroprotective effects and increased cellular ATP levels compared with those of 1.

Keywords: 11α-Hydroxyprogesterone; Cytotoxicity; Glucosylation; Neuroprotective activity; Rotenone-induced apoptosis; Steroid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biotransformation
  • Glucosides / chemistry*
  • Glucosyltransferases / metabolism*
  • Hydroxyprogesterones / chemistry*
  • Hydroxyprogesterones / metabolism*
  • Hydroxyprogesterones / pharmacology
  • Neuroprotective Agents / chemistry*
  • Neuroprotective Agents / metabolism*
  • Neuroprotective Agents / pharmacology
  • PC12 Cells
  • Rats

Substances

  • Glucosides
  • Hydroxyprogesterones
  • Neuroprotective Agents
  • Glucosyltransferases