Data-Driven Approaches Used for Compound Library Design for the Treatment of Parkinson's Disease.

Parkinson's disease (PD) is the second most common neurodegenerative disease in older individuals worldwide. Pharmacological treatment for such a disease consists of drugs such as monoamine oxidase B (MAO-B) inhibitors to increase dopamine concentration in the brain. However, such drugs have adverse reactions that limit their use for extended periods; thus, the design of less toxic and more efficient compounds may be explored. In this context, cheminformatics and computational chemistry have recently contributed to developing new drugs and the search for new therapeutic targets. Therefore, through a data-driven approach, we used cheminformatic tools to find and optimize novel compounds with pharmacological activity against MAO-B for treating PD. First, we retrieved from the literature 3316 original articles published between 2015-2021 that experimentally tested 215 natural compounds against PD. From such compounds, we built a pharmacological network that showed rosmarinic acid, chrysin, naringenin, and cordycepin as the most connected nodes of the network. From such compounds, we performed fingerprinting analysis and developed evolutionary libraries to obtain novel derived structures. We filtered these compounds through a docking test against MAO-B and obtained five derived compounds with higher affinity and lead likeness potential. Then we evaluated its antioxidant and pharmacokinetic potential through a docking analysis (NADPH oxidase and CYP450) and physiologically-based pharmacokinetic (PBPK modeling). Interestingly, only one compound showed dual activity (antioxidant and MAO-B inhibitors) and pharmacokinetic potential to be considered a possible candidate for PD treatment and further experimental analysis.

Unraveling the Neuroprotective Effect of Natural Bioactive Compounds Involved in the Modulation of Ischemic Stroke by Network Pharmacology.

Ischemic stroke (IS) is one of the leading causes of mortality worldwide. It is characterized by the partial or total occlusion of arteries that supply blood to the brain, leading to the death of brain cells. In recent years, natural bioactive compounds (NBCs) have shown properties that ameliorate the injury after IS and improve the patient's outcome, which has proven to be a potential therapeutic strategy due to their neuroprotective effects. Hence, in the present study, we use both systems pharmacology and chemoinformatic analyses to identify which NBCs have the most potential to be used against IS in clinics. Our results identify that flavonoids and terpenoids are the most studied NBCs, and, mainly, salidrosides, ginkgolides A, B, C, and K, cordycepin, curcumin, baicalin, resveratrol, fucose, and cannabidiol, target the main pathological processes occurring in IS. However, the medicinal chemistry properties of such compounds demonstrate that only six fulfill such criteria. However, only cordycepin and salidroside possess properties as leader molecules, suggesting that these compounds may be considered in developing novel drugs against IS.