Biotransformation into 11α-hydroxyprogesterone glucosides by glucosyltransferase

Area of Science:

• Neuroscience
• Endocrinology
• Biochemistry

Background:

• Steroidal hormone activity in the brain is gaining research interest.
• Glucosides are discussed as synthetic precursors for glucuronide labeling.
• 11α-hydroxyprogesterone is a known blood pressure regulator, but its anti-androgen activity is unexplored.

Purpose of the Study:

• To synthesize novel 11α-hydroxyprogesterone glucosides.
• To characterize the structure of these synthesized glucosides.
• To evaluate the neuroprotective potential of these glucosides in vitro.

Main Methods:

• Enzymatic synthesis of glucosides using UDP-glucosyltransferase.
• Structural elucidation via high-resolution mass spectrometry and various NMR techniques (1D and 2D).
• In vitro bioactivity testing on rotenone-induced PC12 cells.

Main Results:

• Successfully synthesized two 11α-hydroxyprogesterone glucosides: 11α-(β-d-glucopyranosyl)oxyprogesterone (2) and 11α-(β-d-laminaribiosyl)oxyprogesterone (3).
• Confirmed structures using advanced analytical methods like HR-QTOF-ESI-MS and comprehensive NMR analysis.
• Compounds 2 and 3 exhibited superior neuroprotective effects and increased cellular ATP levels compared to the parent compound 1 in rotenone-induced PC12 cells.

Conclusions:

• Novel 11α-hydroxyprogesterone glucosides (2 and 3) were synthesized and structurally characterized.
• These glucosides display significant neuroprotective properties and enhance cellular ATP levels.
• The findings suggest potential therapeutic applications for these compounds in neurodegenerative conditions.