Journal of Alzheimer's disease : JAD · 2025
In silico study of selected alkaloids as dual inhibitors of β- and γ-secretases for Alzheimer's disease.
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Onifade Isreal Ayobami, Umar Haruna Isiyaku, Aborode Abdullahi Tunde, Awaji Aeshah A, Jegede Ifeoluwapo Deborah, Adeleye Bunmi Helen, Fatoba Dorcas Oladayo, Bello Ridwan Opeyemi, Fakorede Sodiq, Idowu Nike
Аннотация
BACKGROUND: Alzheimer's disease (AD) has become common as the number of aged people increases making it as a socioeconomic problem lately. To date, no success is recorded for disease-modifying therapies for AD but only drugs for symptomatic relief exist. Research has been centered on the role of amyloid-β on the pathogenesis of AD, which has led to the development of drugs that target Aβ (β- and γ-secretase inhibitors) to reduce the amount of Aβ formed. However, the existing β and γ-secretase inhibitors were associated with harmful side effects, low efficacy, and inability to cross the blood-brain barrier.
OBJECTIVE: This study therefore used in silico approach to predict the inhibitory properties of alkaloids as potential drug targets against AD.
METHODS: Thus, in this current study, 54 alkaloids from the PhytoHub server (phytohub.eu), and two approved drugs were docked against β-secretases. Additionally, galantamine and 5 alkaloids with the utmost binding potential with β-secretase were subjected to pharmacokinetics evaluation and docked against γ-secretase.
RESULTS: From the result, 5 compounds displayed for both docking periods, with demissidine, solasodine, tomatidine, and solanidine having better BE than the control drugs. Based on the pharmacokinetics evaluation, 4 compounds possessed good pharmacokinetic evaluation and biological activities than galantamine.
CONCLUSIONS: This study suggests that demissidine, solasodine, tomatidine, and solanidine are promising dual inhibitors against β- and γ-secretase proteins in silico. However, there is an urgent need to carry out in vitro and in vivo experiments on these new leads to validate the findings of this study.
OBJECTIVE: This study therefore used in silico approach to predict the inhibitory properties of alkaloids as potential drug targets against AD.
METHODS: Thus, in this current study, 54 alkaloids from the PhytoHub server (phytohub.eu), and two approved drugs were docked against β-secretases. Additionally, galantamine and 5 alkaloids with the utmost binding potential with β-secretase were subjected to pharmacokinetics evaluation and docked against γ-secretase.
RESULTS: From the result, 5 compounds displayed for both docking periods, with demissidine, solasodine, tomatidine, and solanidine having better BE than the control drugs. Based on the pharmacokinetics evaluation, 4 compounds possessed good pharmacokinetic evaluation and biological activities than galantamine.
CONCLUSIONS: This study suggests that demissidine, solasodine, tomatidine, and solanidine are promising dual inhibitors against β- and γ-secretase proteins in silico. However, there is an urgent need to carry out in vitro and in vivo experiments on these new leads to validate the findings of this study.