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

Sabrina Taliani; Federico Da Settimo; Claudia Martini; Sonia Laneri; Ettore Novellino; Giovanni Greco

doi:10.3390/molecules25102331

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

Molecules. 2020 May 16;25(10):2331. doi: 10.3390/molecules25102331.

Authors

Sabrina Taliani¹, Federico Da Settimo¹, Claudia Martini¹, Sonia Laneri², Ettore Novellino², Giovanni Greco²

Affiliations

¹ Department of Pharmacy, University of Pisa, Via Bonanno Pisano, 6, 56126 Pisa, Italy.
² Department of Pharmacy, University of Naples "Federico II", Via D. Montesano, 49, 80131 Naples, Italy.

Abstract

Several indole derivatives have been disclosed by our research groups that have been collaborating for nearly 25 years. The results of our investigations led to a variety of molecules binding selectively to different pharmacological targets, specifically the type A γ-aminobutyric acid (GABA_A) chloride channel, the translocator protein (TSPO), the murine double minute 2 (MDM2) protein, the A_2B adenosine receptor (A_2B AR) and the Kelch-like ECH-associated protein 1 (Keap1). Herein, we describe how these works were conceived and carried out thanks to the versatility of indole nucleus to be exploited in the design and synthesis of drug-like molecules.

Keywords: A2B adenosine receptor (A2B AR); Kelch-like ECH-associated protein 1 (Keap1); murine double Minute 2 (MDM2) protein; translocator protein (TSPO); type A γ-aminobutyric acid (GABAA) chloride channel.

Publication types

Review

MeSH terms

Animals
Diazepam / analogs & derivatives*
Diazepam / pharmacology
Drug Design*
GABA Modulators / chemical synthesis*
GABA Modulators / pharmacology
Humans
Indoles / chemical synthesis*
Indoles / pharmacology
Kelch-Like ECH-Associated Protein 1 / agonists
Kelch-Like ECH-Associated Protein 1 / antagonists & inhibitors
Kelch-Like ECH-Associated Protein 1 / metabolism
Ligands
Mice
Protein Binding
Proto-Oncogene Proteins c-mdm2 / antagonists & inhibitors
Proto-Oncogene Proteins c-mdm2 / chemistry
Proto-Oncogene Proteins c-mdm2 / metabolism
Receptor, Adenosine A2B / chemistry
Receptor, Adenosine A2B / metabolism
Receptors, GABA / chemistry
Receptors, GABA / metabolism
Receptors, GABA-A / chemistry
Receptors, GABA-A / metabolism*
Structure-Activity Relationship

Substances

GABA Modulators
Indoles
KEAP1 protein, human
Kelch-Like ECH-Associated Protein 1
Ligands
Receptor, Adenosine A2B
Receptors, GABA
Receptors, GABA-A
TSPO protein, human
MDM2 protein, human
Mdm2 protein, mouse
Proto-Oncogene Proteins c-mdm2
Diazepam