An in silico study of binding of new lutein esters to nuclear endocrine receptors

Here we present the results of an in silico bioactivity study of 13 structurally diverse lutein diesters that were previously synthesized in the laboratory to improve the inherently poor chemical stability of lutein, an important food nutrient. Using predictive models, we aimed to identify potential receptor-related activity patterns relevant to endocrine signalling. Because orally administered lutein diesters may undergo partial or complete gastrointestinal hydrolysis before absorption, the corresponding carboxylic acids were also evaluated as potentially relevant exposure forms. Most lutein esters showed predicted receptor-activity classifications similar to lutein, whereas esters containing long-chain fatty acid moieties showed more distinct prediction patterns. Lutein di(pentafluoropropanoate) is of particular concern because it readily hydrolyses, releasing pentafluoropropionic acid, a corrosive hydrolysis product. The remaining carboxylic acids were not classified as notably concerning within the scope of the applied prediction models. Overall, the results identify lutein esters that merit further investigation as candidate stabilized lutein derivatives, while highlighting specific structures that should be prioritized for targeted experimental follow-up. • In silico screening identified most lutein diesters with activities similar to lutein. • Long-chain and perfluorinated derivatives showed more distinct prediction patterns. • Intact esters and hydrolysis products were assessed with complementary models. • Results support first-step prioritization for further experimental evaluation.