Abstract
The mitochondrial translocator protein (TSPO) mediates the synthesis of neurosteroids in the CNS, which have been demonstrated to enhance the neurotransmitter GABA response, exhibiting related behavioural properties. Selective TSPO ligands are able to stimulate steroidogenesis with great efficacy, thus representing potential anxiolytic agents. This review describes the development of a class of high affinity ligands to TSPO, N,N-dialkylindol-3-ylglyoxylamides (IGA), from the initial stages of design to the pharmacological characterization of selected compounds for their anxiolytic activity. Affinity data and SARs of the new class of ligands are discussed; the potential applications of compounds characterized by the indolylglyoxylyl scaffold in diagnostic imaging are also pointed out.
Keywords: Anxiolytic activity, binding affinity, neurosteroids, 2-phenylindolylglyoxylamides, pregnenolone, SARs, TSPO ligands, Translocator protein (TSPO), Anxiety and sleep disorders, “central benzodiazepine receptor” (CBR), rebound syndrome, voltage-dependent anion channel (VDAC)
Current Topics in Medicinal Chemistry
Title: Medicinal Chemistry of Indolylglyoxylamide TSPO High Affinity Ligands with Anxiolytic-Like Effects
Volume: 12 Issue: 4
Author(s): Francesca Simorini, Anna Maria Marini, Sabrina Taliani, Concettina La Motta, Silvia Salerno, Isabella Pugliesi and Federico Da Settimo
Affiliation:
Keywords: Anxiolytic activity, binding affinity, neurosteroids, 2-phenylindolylglyoxylamides, pregnenolone, SARs, TSPO ligands, Translocator protein (TSPO), Anxiety and sleep disorders, “central benzodiazepine receptor” (CBR), rebound syndrome, voltage-dependent anion channel (VDAC)
Abstract: The mitochondrial translocator protein (TSPO) mediates the synthesis of neurosteroids in the CNS, which have been demonstrated to enhance the neurotransmitter GABA response, exhibiting related behavioural properties. Selective TSPO ligands are able to stimulate steroidogenesis with great efficacy, thus representing potential anxiolytic agents. This review describes the development of a class of high affinity ligands to TSPO, N,N-dialkylindol-3-ylglyoxylamides (IGA), from the initial stages of design to the pharmacological characterization of selected compounds for their anxiolytic activity. Affinity data and SARs of the new class of ligands are discussed; the potential applications of compounds characterized by the indolylglyoxylyl scaffold in diagnostic imaging are also pointed out.
Export Options
About this article
Cite this article as:
Simorini Francesca, Maria Marini Anna, Taliani Sabrina, La Motta Concettina, Salerno Silvia, Pugliesi Isabella and Da Settimo Federico, Medicinal Chemistry of Indolylglyoxylamide TSPO High Affinity Ligands with Anxiolytic-Like Effects, Current Topics in Medicinal Chemistry 2012; 12 (4) . https://dx.doi.org/10.2174/156802612799078766
DOI https://dx.doi.org/10.2174/156802612799078766 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Adaptogens—History and Future Perspectives
Adaptogens are pharmacologically active compounds or plant extracts that are associated with the ability to enhance the body’s stability against stress. The intake of adaptogens is associated not only with a better ability to adapt to stress and maintain or normalise metabolic functions but also with better mental and physical ...read more
Addressing the Most Common Causes of Death with Niacin/NAD and Inositol Polyphosphates
The most common causes of death in the world are cardiovascular disease (CVD) and cancer. These are perhaps best addressed by reducing lipodystrophy and blockages with niacin and inositol polyphosphates (e.g., IP6+inositol) respectively when addressing CVD. Niacin serves as a vitamin by virtue of its role as a skeletal precursor ...read more
AlphaFold in Medicinal Chemistry: Opportunities and Challenges
AlphaFold, a groundbreaking AI tool for protein structure prediction, is revolutionizing drug discovery. Its near-atomic accuracy unlocks new avenues for designing targeted drugs and performing efficient virtual screening. However, AlphaFold's static predictions lack the dynamic nature of proteins, crucial for understanding drug action. This is especially true for multi-domain proteins, ...read more
Artificial intelligence for Natural Products Discovery and Development
Our approach involves using computational methods to predict the potential therapeutic benefits of natural products by considering factors such as drug structure, targets, and interactions. We also employ multitarget analysis to understand the role of drug targets in disease pathways. We advocate for the use of artificial intelligence in predicting ...read more

- Author Guidelines
- Bentham Author Support Services (BASS)
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Nanoparticles in Cancer
Current Radiopharmaceuticals Unveiling the Molecular Mechanism of Diosmetin and its Impact on Multifaceted Cellular Signaling Pathways
Protein & Peptide Letters Longitudinal Melatonin Production in Female Laboratory Rats During 1997-2006: Possible Modulatory Effects of Changing Solar Activity
Current Aging Science Protein Kinases as Drug Targets in Human and Animal Diseases
Current Enzyme Inhibition Marine Derived Anticancer Drugs Targeting Microtubule
Recent Patents on Anti-Cancer Drug Discovery Molecular Markers of Angiogenesis and Metastasis in Lines of Oral Carcinoma after Treatment with Melatonin
Anti-Cancer Agents in Medicinal Chemistry Non-Homologous DNA End Joining in Anticancer Therapy
Current Cancer Drug Targets Destroying RNA as a Therapeutic Approach
Current Medicinal Chemistry Marine Natural Products and Related Compounds as Anticancer Agents: an Overview of their Clinical Status
Anti-Cancer Agents in Medicinal Chemistry Peptido-Targeting of the Mitochondrial Transition Pore Complex for Therapeutic Apoptosis Induction
Current Pharmaceutical Design SnoN: Bridging Neurobiology and Cancer Biology
Current Molecular Medicine Uncertainty in the Translation of Preclinical Experiments to Clinical Trials. Why do Most Phase III Clinical Trials Fail?
Current Gene Therapy Macroautophagy as a Target of Cancer Therapy
Current Cancer Therapy Reviews Patents in Cancer Stem Cells
Recent Patents on Biomarkers Metabotropic Glutamate Receptors: A Review on Prospectives and Therapeutic Aspects
Mini-Reviews in Medicinal Chemistry Medulloblastoma: Role of Developmental Pathways, DNA Repair Signaling, and Other Players
Current Molecular Medicine C-glycosyl Flavone from Urginea indica Inhibits Growth and Dissemination of Ehrlich Ascites Carcinoma Cells in Mice
Anti-Cancer Agents in Medicinal Chemistry Recent Findings on the Application of Toll-like Receptors Agonists in Cancer Therapy
Current Medicinal Chemistry Role of Early Growth Response-1 in the Development of Alcohol-Induced Steatosis
Current Molecular Pharmacology Anti-Carcinogenic Effects of Carnosol-An Updated Review
Current Drug Discovery Technologies