Advances in bile acid medicinal chemistry

Area of Science:

• Biochemistry
• Medicinal Chemistry
• Pharmacology

Background:

• Bile acids (BAs) are cholesterol-derived steroidal molecules synthesized in the liver.
• Traditionally recognized for aiding lipid absorption, BAs are now known as ligands for farnesoid X receptor (FXR) and TGR5.
• BAs influence lipid and glucose homeostasis, and exhibit diverse effects on inflammatory, apoptotic, and carcinogenic signaling pathways.

Purpose of the Study:

• To review recent advancements in the medicinal chemistry of bile acids.
• To highlight the therapeutic potential of bile acid derivatives across various medical fields.

Main Methods:

• Literature review of recent developments in bile acid research.
• Analysis of medicinal chemistry programs targeting bile acid derivatives.

Main Results:

• Bile acids regulate metabolic and inflammatory processes via FXR and TGR5.
• BAs show neuroprotective potential, relevant to Huntington's and Alzheimer's diseases.
• Medicinal chemistry efforts are yielding BA derivatives for metabolic disorders, cancer, infections, glaucoma, and inflammation.

Conclusions:

• Bile acid biology has expanded significantly beyond its digestive functions.
• Bile acid derivatives represent promising therapeutic leads for a wide range of diseases.
• Further research in bile acid medicinal chemistry holds significant potential for novel drug development.