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Rational Design and Greener Synthesis of Selenylated Indolamides as Potential Anti-Alzheimer’s Agents

Year: 2025

Type: article

Abstract: High Resolution Image Download MS PowerPoint Slide This study presents the rational design and sustainable synthesis of selenylated indolamides as potential therapeutic agents for Alzheimer’s disease. Through computational approaches, including molecular docking and pharmacokinetic analyses, we identified key structural modifications that improve acetylcholinesterase inhibition, a critical target for AD treatment. We employed an environmentally benign I 2 /DMSO oxidation system to optimize the synthetic protocol, enabling the efficient selenylation of 27 indolamide derivatives ( 5a–6a ) via a straightforward and practical transformation, delivering high yields of up to 99%. Importantly, the methodology proved scalable, delivering an 88% yield on a gram-scale reaction. In silico ADMET predictions using the pkCSM platform indicated that C2-selenylated indolamides possess an improved safety profile and promising pharmacokinetic properties, suggesting their potential for further drug development. In particular, compounds 5a and 5y demonstrated the best balance between reaction yield and docking score (94% and 86.17; 98% and 93.71, respectively). These findings highlight the significance of incorporating green chemistry principles alongside advanced in silico methodologies to drive innovation in drug discovery.

Source: ACS Omega

DOI: 10.1021/acsomega.5c08265

Authors: Angélica Justino Dias, Aldo Sena Oliveira, Angélica Ceci Silva, Antonio Luiz Braga

Institutions: Universidade Federal de Santa Catarina, University of Lisbon, Gulbenkian Institute for Molecular Medicine

Language: English

Topic: Cholinesterase and Neurodegenerative Diseases

Subfield: Pharmacology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $1,935