Exploiting the Indole Scaffold to Design Compounds Binding to Different Pharmacological Targets

Area of Science:

• Medicinal Chemistry
• Organic Synthesis
• Pharmacology

Background:

• Indole derivatives are a significant class of heterocyclic compounds with diverse biological activities.
• Our research groups have a long-standing collaboration focused on indole chemistry.

Purpose of the Study:

• To explore the synthetic versatility of the indole nucleus for drug-like molecule design.
• To identify novel indole derivatives with selective binding affinities for various pharmacological targets.

Main Methods:

• Design and synthesis of novel indole derivatives.
• Pharmacological evaluation of synthesized compounds.
• Structure-activity relationship (SAR) studies.

Main Results:

• Several indole derivatives were synthesized and characterized.
• Selective binding of these derivatives to the type A γ-aminobutyric acid (GABA_A) chloride channel, translocator protein (TSPO), murine double minute 2 (MDM2) protein, A_2B adenosine receptor (A_2B AR), and Kelch-like ECH-associated protein 1 (Keap1) was achieved.
• Demonstrated the utility of the indole scaffold in developing targeted therapeutics.

Conclusions:

• The indole nucleus is a versatile scaffold for the development of drug candidates.
• The synthesized indole derivatives show promise for targeting a range of important biological pathways.
• This work underscores the success of long-term collaborative research in medicinal chemistry.