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Journal Article Review Epublish 8 citations

PubMed: 40430428 DOI: 10.3390/ph18050607

Quinoline Quest: Kynurenic Acid Strategies for Next-Generation Therapeutics via Rational Drug Design.

Pharmaceuticals (Basel) 18(5)

Authors: Masaru Tanaka, István Szatmári, László Vécsei

Affiliations

  • Danube Neuroscience Research Laboratory, HUN-REN-SZTE Neuroscience Research Group, Hungarian Research Network, University of Szeged (HUN-REN-SZTE), Tisza Lajos krt. 113, H-6725 Szeged, Hungary.
  • Institute of Pharmaceutical Chemistry and HUN-REN-SZTE Stereochemistry Research Group, University of Szeged, Eötvös u. 6, H-6720 Szeged, Hungary.
  • Department of Neurology, Albert Szent-Györgyi Medical School, University of Szeged, Semmelweis u. 6, H-6725 Szeged, Hungary.

Abstract

BACKGROUND

Quinoline-derived metabolites exhibit notable chemical complexity. What causes minor structural alterations to induce significant changes in disease outcomes? Historically, eclipsed by more straightforward scaffolds, these chemicals serve as a dynamic hub in tryptophan metabolism, linking immunomodulation, excitotoxicity, and cancer. However, many of these compounds struggle to cross the blood-brain barrier, and we still do not fully understand how certain structural changes affect their bioavailability or off-target effects. Thus, contemporary research highlights halogenation, esterification, and computational modeling to enhance structure-activity relationships.

SUMMARY

This narrative review emphasizes the integration of rational drug design, multi-target ligands, and prodrug methods in enhancing quinoline scaffolds. We explore each molecule's therapeutic promise, refine each scaffold's design, and develop each derivative to maximize clinical utility. Translating these laboratory findings into clinical practice, however, remains a formidable challenge.

CONCLUSIONS

Through the synthesis of findings regarding NMDA receptor antagonism, improved oral bioavailability, and reduced metabolic instability, we demonstrate how single-site changes might modulate excitotoxicity and immunological signaling. Advancing quinoline-based medicines will yield significant advancements in neurology, psychiatry, and oncology. This enlarged framework fosters collaborative discovery, engages various audiences, and advances the field towards next-generation disease-modifying therapies. Robust preclinical validation, patient classification, and comprehensive toxicity evaluations are crucial stages for achieving these extensive endeavors and fostering future therapeutic discoveries globally.

MeSH

Biological Availability, Pharmaceutical Preparations, Drug Design, Neuroprotection, Therapeutics, Kynurenic Acid, Pharmacokinetics

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