Natural products in combinatorial chemistry: an andrographolide-based library

Area of Science:

• Medicinal Chemistry
• Natural Product Synthesis
• Drug Discovery

Background:

• Andrographolide, a natural product, serves as a valuable scaffold for drug discovery.
• The development of diverse compound libraries is crucial for identifying novel therapeutic agents.
• Efficient synthetic strategies are needed to access complex natural product derivatives.

Purpose of the Study:

• To generate a novel natural-product-based library starting from andrographolide.
• To explore chemical space around andrographolide through parallel synthesis.
• To ensure the pharmacological relevance of synthesized compounds via virtual assessment.

Main Methods:

• Parallel solution-phase synthesis utilizing andrographolide as the starting material.
• Ozonolysis for initial transformation, followed by introduction of a thiazole moiety.
• Decoration at two points of diversity to create natural product derivatives.
• Virtual library generation and physicochemical property assessment for compound selection.

Main Results:

• A library of 360 distinct natural product derivatives was successfully synthesized.
• The synthetic route enabled efficient decoration of the andrographolide scaffold.
• Virtual screening identified compounds with desirable physicochemical properties for potential pharmacological activity.

Conclusions:

• The described methodology provides a robust platform for generating diverse andrographolide-based compound libraries.
• The approach ensures the selection of compounds with high potential for pharmacological relevance.
• This library serves as a valuable resource for further drug discovery efforts.