Natural products as a major source of candidates for potential senolytic compounds obtained by in silico screening

Autor: Gil A. Magos-Guerrero, Oscar S. Barrera-Vázquez, Juan L. Escobar-Ramírez, Juan C. Gomez-Verjan
Rok vydání: 2022
Předmět:
Zdroj: Medicinal chemistry (Shariqah (United Arab Emirates)).
ISSN: 1875-6638
Popis: Background: Preclinical studies suggest that senolytic compounds such as quercetin (a natural product) and dasatinib (a synthetic product) decrease senescent cells, reduce inflammation, and alleviate human frailty. This evidence has opened a new field of research for studying the effect of these compounds on age-related dysfunction and diseases. Objective: The present study performed in silico and we identified new potential senolytic candidates from an extensive database that contains natural products (NPs) and semi-synthetic products (SMSs). Methods: Computer programs Chemminer and rcdk packages, which compared the fingerprints of numerous molecules (40,383) with reference senolytics, and the creation of a pharmacological network built with signaling pathways and targets involved in senescence processes were used to identify compounds with a potential activity. Results: Six drug-like candidates (3,4'-dihydroxypropiophenone, baicalein, α, β-dehydrocurvularin, lovastatin, luteolin, and phloretin) were identified. Conclusion: To our knowledge, this is the first time that these six natural molecules have been proposed to have senolytic activity. To validate the methodology employed in the identification of new drug-like senolytics, experimental evidence is needed with models that evaluate senolytic activity.
Databáze: OpenAIRE