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

Abstract

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 frailty in humans. This evidence has opened a new field of research for studying the effect of these compounds on age-related dysfunction and diseases. Objective: In the present study performed in silico, we identified new potentially 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 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 most likely 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.