Work

Sustainable Synthesis of 3‐(1 H ‐Indol‐3‐yl)propionic Acid Derivatives with Anti‐Alzheimer Activity

Year: 2026

Type: article

Abstract: A biocatalytic approach was applied to synthesizing esters and amides derived from 2-(1H-indol-3-yl)acetic (IAA), 3-(1H-indol-3-yl)propionic (IPA), and 4-(1H-indol-3-yl)butanoic (IBA) acids. Thirty-seven derivatives were obtained through lipase catalysis in mild reaction conditions with good to excellent yields and a reduced environmental impact. The scope of the reaction was explored in terms of enzyme source, solvent, temperature, substrate-to-nucleophile and enzyme-to-substrate ratios, and substrate versatility. Ten representative derivatives were evaluated as potential anti-Alzheimer's disease (AD) agents using Caenorhabditis elegans models. Among them, octyl 3-(1H-indol-3-yl)propanoate (6e), N-butyl-3-(1H-indol-3-yl)propanamide (10a), and (S)-N-(2-hydroxypropyl)-3-(1H-indol-3-yl)propanamide (13c) emerged as the most promising candidates, demonstrating significant improvements in AD pathology, including enhanced locomotion and mitochondrial function. In addition, the obtained compounds showed no toxicity in Vero cells, making them potential lead drug candidates.

Source: ChemMedChem

DOI: 10.1002/cmdc.70395

Authors: Fabricio Freije García, Carmen Martínez‐Fernandez, Christian Griñán Ferré, Guadalupe García Liñares

Institutions: Universidad de Buenos Aires, Universitat de Barcelona, Instituto de Salud Carlos III, Biomedical Research Networking Center on Neurodegenerative Diseases

Language: English

Topic: Enzyme Catalysis and Immobilization

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

Funders: Consejo Nacional de Investigaciones Científicas y Técnicas, Universidad de Buenos Aires, Secretaría de Ciencia y Técnica, Universidad de Buenos Aires