Ultrasound-Assisted Synthesis of Pyrazoline Derivatives as Potential Antagonists of RAGE-Mediated Pathologies: Insights from SAR Studies and Biological Evaluations.

Anca-Elena Dascălu, Christophe Furman, Steve Lancel, Emmanuelle Lipka, Maxime Liberelle, Eric Boulanger, Alina Ghinet

Health and Environment, Laboratory of Sustainable Chemistry and Health, Junia, F-59000, Lille, France.Health and Environment, Laboratory of Sustainable Chemistry and Health, Junia, F-59000, Lille, France. · pubmed

Paper

Abstract

In the context of age-related disorders, the receptor of advanced glycation end products (RAGE), plays a pivotal role in the pathogenesis of these conditions by triggering downstream signaling pathways associated with chronic inflammation and oxidative stress. Targeting this inflammaging phenomenon with RAGE antagonists holds promise for interventions with broad implications in healthy aging and the management of age-related conditions. This study explores the structure-activity relationship (SAR) of pyrazoline-based RAGE antagonists synthesized using an ultrasound-assisted green one-pot two-steps methodology. Our investigation identifies phenylurenyl-pyrazoline 2 g as a promising candidate, demonstrating superior efficiency compared to the reference antagonist Azeliragon (IC

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Research summary

The paper addresses the role of RAGE in age-related disorders and explores potential antagonists that could mitigate chronic inflammation and oxidative stress, which are key factors in the aging process. However, while it presents a novel synthesis method and identifies a promising candidate, the findings appear to be incremental rather than groundbreaking, limiting its overall impact on the field of longevity research.

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