Exploring the anti-gout potential of sunflower receptacles alkaloids: A computational and pharmacological analysis.
Comput Biol Med
; 172: 108252, 2024 Apr.
Article
em En
| MEDLINE
| ID: mdl-38493604
ABSTRACT
Gout, a painful condition marked by elevated uric acid levels often linked to the diet's high purine and alcohol content, finds a potential treatment target in xanthine oxidase (XO), a crucial enzyme for uric acid production. This study explores the therapeutic properties of alkaloids extracted from sunflower (Helianthus annuus L.) receptacles against gout. By leveraging computational chemistry and introducing a novel R-based clustering algorithm, "TriDimensional Hierarchical Fingerprint Clustering with Tanimoto Representative Selection (3DHFC-TRS)," we assessed 231 alkaloid molecules from sunflower receptacles. Our clustering analysis pinpointed six alkaloids with significant gout-targeting potential, particularly emphasizing the fifth cluster's XO inhibition capabilities. Through molecular docking and the BatchDTA prediction model, we identified three top compounds-2-naphthylalanine, medroxalol, and fenspiride-with the highest XO affinity. Further molecular dynamics simulations assessed their enzyme active site interactions and binding free energies, employing MM-PBSA calculations. This investigation not only highlights the discovery of promising compounds within sunflower receptacle alkaloids via LC-MS but also introduces medroxalol as a novel gout treatment candidate, showcasing the synergy of computational techniques and LC-MS in drug discovery.
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1
Base de dados:
MEDLINE
Assunto principal:
Etanolaminas
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Gota
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Helianthus
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article