The Molecular Biological Mechanism of Hydrogen Therapy and Its Application in Spinal Cord Injury.

Hydrogen, which is a novel biomedical molecule, is currently the subject of extensive research involving animal experiments and in vitro cell experiments, and it is gradually being applied in clinical settings. Hydrogen has been proven to possess anti-inflammatory, selective antioxidant, and antiapoptotic effects, thus exhibiting considerable protective effects in various diseases. In recent years, several studies have provided preliminary evidence for the protective effects of hydrogen on spinal cord injury (SCI). This paper provides a comprehensive review of the potential molecular biology mechanisms of hydrogen therapy and its application in treating SCI, with an aim to better explore the medical value of hydrogen and provide new avenues for the adjuvant treatment of SCI.

Emerging ferroptosis inhibitors as a novel therapeutic strategy for the treatment of neonatal hypoxic-ischemic encephalopathy.

Neonatal hypoxia-ischemia encephalopathy (NHIE), an oxygen deprivation-mediated brain injury due to birth asphyxia or reduced cerebral blood perfusion, often leads to lifelong sequelae, including seizures, cerebral palsy, and mental retardation. NHIE poses a significant health challenge, as one of the leading causes of neonatal morbidity and mortality globally. Despite this, available therapies are limited. Numerous studies have recently demonstrated that ferroptosis, an iron-dependent non-apoptotic regulated form of cell death characterized by lipid peroxidation (LPO) and iron dyshomeostasis, plays a role in the genesis of NHIE. Moreover, recently discovered compounds have been shown to exert potential therapeutic effects on NHIE by inhibiting ferroptosis. This comprehensive review summarizes the fundamental mechanisms of ferroptosis contributing to NHIE. We focus on various emerging therapeutic compounds exhibiting characteristics of ferroptosis inhibition and delineate their pharmacological benefits for the treatment of NHIE. This review suggests that pharmacological inhibition of ferroptosis may be a potential therapeutic strategy for NHIE.

Lead optimization based design, synthesis, and pharmacological evaluation of quinazoline derivatives as multi-targeting agents for Alzheimer's disease treatment.

The complexity and multifaceted nature of Alzheimer's disease (AD) have driven us to further explore quinazoline scaffolds as multi-targeting agents for AD treatment. The lead optimization strategy was utilized in designing of new series of derivatives (AK-1 to AK-14) followed by synthesis, characterization, and pharmacological evaluation against human cholinesterase's (hChE) and ß-secretase (hBACE-1) enzymes. Amongst them, compounds AK-1, AK-2, and AK-3 showed good and significant inhibitory activity against both hAChE and hBACE-1 enzymes with favorable permeation across the blood-brain barrier. The most active compound AK-2 revealed significant propidium iodide (PI) displacement from the AChE-PAS region and was non-neurotoxic against SH-SY5Y cell lines. The lead molecule (AK-2) also showed Aß aggregation inhibition in a self- and AChE-induced Aß aggregation, Thioflavin-T assay. Further, compound AK-2 significantly ameliorated Aß-induced cognitive deficits in the Aß-induced Morris water maze rat model and demonstrated a significant rescue in eye phenotype in the Aꞵ-phenotypic drosophila model of AD. Ex-vivo immunohistochemistry (IHC) analysis on hippocampal rat brains showed reduced Aß and BACE-1 protein levels. Compound AK-2 suggested good oral absorption via pharmacokinetic studies and displayed a good and stable ligand-protein interaction in in-silico molecular modeling analysis. Thus, the compound AK-2 can be regarded as a lead molecule and should be investigated further for the treatment of AD.

The Benzoylpiperidine Fragment as a Privileged Structure in Medicinal Chemistry: A Comprehensive Review.

The phenyl(piperidin-4-yl)methanone fragment (here referred to as the benzoylpiperidine fragment) is a privileged structure in the development of new drugs considering its presence in many bioactive small molecules with both therapeutic (such as anti-cancer, anti-psychotic, anti-thrombotic, anti-arrhythmic, anti-tubercular, anti-parasitic, anti-diabetic, and neuroprotective agents) and diagnostic properties. The benzoylpiperidine fragment is metabolically stable, and it is also considered a potential bioisostere of the piperazine ring, thus making it a feasible and reliable chemical frame to be exploited in drug design. Herein, we discuss the main therapeutic and diagnostic agents presenting the benzoylpiperidine motif in their structure, covering articles reported in the literature since 2000. A specific section is focused on the synthetic strategies adopted to obtain this versatile chemical portion.

Protection of Si Nanowires against Aß Toxicity by the Inhibition of Aß Aggregation.

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by the accumulation of amyloid beta (Aß) plaques in the brain. Aß1-42 is the main component of Aß plaque, which is toxic to neuronal cells. Si nanowires (Si NWs) have the advantages of small particle size, high specific surface area, and good biocompatibility, and have potential application prospects in suppressing Aß aggregation. In this study, we employed the vapor-liquid-solid (VLS) growth mechanism to grow Si NWs using Au nanoparticles as catalysts in a plasma-enhanced chemical vapor deposition (PECVD) system. Subsequently, these Si NWs were transferred to a phosphoric acid buffer solution (PBS). We found that Si NWs significantly reduced cell death in PC12 cells (rat adrenal pheochromocytoma cells) induced by Aß1-42 oligomers via double staining with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and fluorescein diacetate/propyl iodide (FDA/PI). Most importantly, pre-incubated Si NWs largely prevented Aß1-42 oligomer-induced PC12 cell death, suggesting that Si NWs exerts an anti-Aß neuroprotective effect by inhibiting Aß aggregation. The analysis of Fourier Transform Infrared (FTIR) results demonstrates that Si NWs reduce the toxicity of fibrils and oligomers by intervening in the formation of ß-sheet structures, thereby protecting the viability of nerve cells. Our findings suggest that Si NWs may be a potential therapeutic agent for AD by protecting neuronal cells from the toxicity of Aß1-42.

Indole-Based Compounds in the Development of Anti-Neurodegenerative Agents.

Neurodegeneration is a gradual decay process leading to the depletion of neurons in both the central and peripheral nervous systems, ultimately resulting in cognitive dysfunctions and the deterioration of brain functions, alongside a decline in motor skills and behavioral capabilities. Neurodegenerative disorders (NDs) impose a substantial socio-economic strain on society, aggravated by the advancing age of the world population and the absence of effective remedies, predicting a negative future. In this context, the urgency of discovering viable therapies is critical and, despite significant efforts by medicinal chemists in developing potential drug candidates and exploring various small molecules as therapeutics, regrettably, a truly effective treatment is yet to be found. Nitrogen heterocyclic compounds, and particularly those containing the indole nucleus, which has emerged as privileged scaffold, have attracted particular attention for a variety of pharmacological applications. This review analyzes the rational design strategy adopted by different research groups for the development of anti-neurodegenerative indole-based compounds which have the potential to modulate various molecular targets involved in NDs, with reference to the most recent advances between 2018 and 2023.

Characterization of Phenolic Compounds in Extra Virgin Olive Oil from Granada (Spain) and Evaluation of Its Neuroprotective Action.

The olive oil sector is a fundamental food in the Mediterranean diet. It has been demonstrated that the consumption of extra virgin olive oil (EVOO) with a high content of phenolic compounds is beneficial in the prevention and/or treatment of many diseases. The main objective of this work was to study the relationship between the content of phenolic compounds and the in vitro neuroprotective and anti-inflammatory activity of EVOOs from two PDOs in the province of Granada. To this purpose, the amounts of phenolic compounds were determined by liquid chromatography coupled to mass spectrometry (HPLC-MS) and the inhibitory activity of acetylcholinesterase (AChE) and cyclooxygenase-2 (COX-2) enzymes by spectrophotometric and fluorimetric assays. The main families identified were phenolic alcohols, secoiridoids, lignans, flavonoids, and phenolic acids. The EVOO samples with the highest total concentration of compounds and the highest inhibitory activity belonged to the Picual and Manzanillo varieties. Statistical analysis showed a positive correlation between identified compounds and AChE and COX-2 inhibitory activity, except for lignans. These results confirm EVOO's compounds possess neuroprotective potential.

The mechanistic interaction, aggregation and neurotoxicity of α-synuclein after interaction with glycyrrhizic acid: Modulation of synucleinopathies.

This article reveals the binding mechanism between glycyrrhizic acid (GA) and α-synuclein to may provide further information for the modulation of synucleinopathies using bioactive compounds. Therefore, the inhibitory activities of GA against α-synuclein aggregation and induced neurotoxicity were evaluated using different assays. Results showed that α-synuclein-GA binding was mediated by intermolecular hydrogen bonds leading to the formation of a slightly folded complex. Theoretical studies revealed that GA binds to the N-terminal domain of α-synuclein and triggers a compact structure around a major part of the N-terminal and the NAC regions along with fluctuations in the C-terminal domain, which are prerequisites for the inhibition of α-synuclein aggregation. Then, the cellular assays showed that GA as a potential small molecule can inhibit the oligomerization of α-synuclein and relevant neurotoxicity through modulation of neural viability, membrane leakage, and ROS formation in a concentration-dependent manner. As a result, the primary mechanism of GA's anti-aggregation and neuroprotective activities is the reorganized α-synuclein structure and fluctuating C-terminal domain, which promotes long-range transient intramolecular contacts between the N-terminal and the C-terminal domain.

Neuroprotective Effect of Sterculia setigera Leaves Hydroethanolic Extract.

Plants are a valuable source of information for pharmacological research and new drug discovery. The present study aimed to evaluate the neuroprotective potential of the leaves of the medicinal plant Sterculia setigera. In vitro, the effect of Sterculia setigera leaves dry hydroethanolic extract (SSE) was tested on cultured cerebellar granule neurons (CGN) survival when exposed to hydrogen peroxide (H2O2) or 6-hydroxydopamine (6-OHDA), using the viability probe fluorescein diacetate (FDA), a lactate dehydrogenase (LDH) activity assay, an immunocytochemical staining against Gap 43, and the quantification of the expression of genes involved in apoptosis, necrosis, or oxidative stress. In vivo, the effect of intraperitoneal (ip) injection of SSE was assessed on the developing brain of 8-day-old Wistar rats exposed to ethanol neurotoxicity by measuring caspase-3 activity on cerebellum homogenates, the expression of some genes in tissue extracts, the thickness of cerebellar cortical layers and motor coordination. In vitro, SSE protected CGN against H2O2 and 6-OHDA-induced cell death at a dose of 10 µg/mL, inhibited the expression of genes Casp3 and Bad, and upregulated the expression of Cat and Gpx7. In vivo, SSE significantly blocked the deleterious effect of ethanol by reducing the activity of caspase-3, inhibiting the expression of Bax and Tp53, preventing the reduction of the thickness of the internal granule cell layer of the cerebellar cortex, and restoring motor functions. Sterculia setigera exerts neuroactive functions as claimed by traditional medicine and should be a good candidate for the development of a neuroprotective treatment against neurodegenerative diseases.

Chemical constituents from stipes of Lentinus edodes and their protective effects against Aß25-35-induced N9 microglia cells injury.

Nine undescribed compounds, along with eight known compounds, were isolated from the stipes of Lentinus edodes. Their structures were established by extensive spectroscopic and circular dichroism analyses. The protective effects against Aß25-35-induced N9 microglia cells injury of these compounds were tested by MTT method, and the levels of apoptosis and ROS were detected by flow cytometry. In addition, the binding sites and interactions of compound with amyloid precursor protein were revealed using molecular docking simulations. These findings further establish the structural diversity and bioactivity of stipes of L. edodes, and provide an experimental basis for targeting Alzheimer's disease as a potential strategy.

Opportunities and perspectives of small molecular phosphodiesterase inhibitors in neurodegenerative diseases.

Phosphodiesterase (PDE) is a superfamily of enzymes that are responsible for the hydrolysis of two second messengers: cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). PDE inhibition promotes the gene transcription by activating cAMP-response element binding protein (CREB), initiating gene transcription of brain-derived neurotrophic factor (BDNF). The procedure exerts neuroprotective profile, and motor and cognitive improving efficacy. From this point of view, PDE inhibition will provide a promising therapeutic strategy for treating neurodegenerative disorders. Herein, we summarized the PDE inhibitors that have entered the clinical trials or been discovered in recent five years. Well-designed clinical or preclinical investigations have confirmed the effectiveness of PDE inhibitors, such as decreasing Aß oligomerization and tau phosphorylation, alleviating neuro-inflammation and oxidative stress, modulating neuronal plasticity and improving long-term cognitive impairment.

Polyphenols from Maackia amurensis Heartwood Protect Neuronal Cells from Oxidative Stress and Prevent Herpetic Infection.

Here, we continued the investigation of anti-HSV-1 activity and neuroprotective potential of 14 polyphenolic compounds isolated from Maackia amurensis heartwood. We determined the absolute configurations of asymmetric centers in scirpusin A (13) and maackiazin (10) as 7R,8R and 1″S,2″S, respectively. We showed that dimeric stilbens maackin (9) and scirpusin A (13) possessed the highest anti-HSV-1 activity among polyphenols 1-14. We also studied the effect of polyphenols 9 and 13 on the early stages of HSV-1 infection. Direct interaction with the virus (virucidal activity) was the main mechanism of the antiviral activity of these compounds. The neuroprotective potential of polyphenolic compounds from M. amurensis was studied using models of 6-hydroxydopamine (6-OHDA)-and paraquat (PQ)-induced neurotoxicity. A dimeric stilbene scirpusin A (13) and a flavonoid liquiritigenin (6) were shown to be the most active compounds among the tested polyphenols. These compounds significantly increased the viability of 6-OHDA-and PQ-treated Neuro-2a cells, elevated mitochondrial membrane potential and reduced the intracellular ROS level. We also found that scirpusin A (13), liquiritigenin (6) and retusin (3) considerably increased the percentage of live Neuro-2a cells and decreased the number of early apoptotic cells. Scirpusin A (13) was the most promising compound possessing both anti-HSV-1 activity and neuroprotective potential.

Geniposide and Harpagoside Functionalized Cerium Oxide Nanoparticles as a Potential Neuroprotective.

Alzheimer's disease is associated with protein aggregation, oxidative stress, and the role of acetylcholinesterase in the pathology of the disease. Previous investigations have demonstrated that geniposide and harpagoside protect the brain neurons, and cerium nanoparticles (CeO2 NPs) have potent redox and antioxidant properties. Thus, the effect of nanoparticles of Ce NPs and geniposide and harpagoside (GH/CeO2 NPs) on ameliorating AD pathogenesis was established on AlCl3-induced AD in mice and an aggregation proteins test in vitro. Findings of spectroscopy analysis have revealed that GH/CeO2 NPs are highly stable, nano-size, spherical in shape, amorphous nature, and a total encapsulation of GH in cerium. Treatments with CeO2 NPs, GH/CeO2 NPs, and donepezil used as positive control inhibit fibril formation and protein aggregation, protect structural modifications in the BSA-ribose system, have the ability to counteract Tau protein aggregation and amyloid-ß1-42 aggregation under fibrillation condition, and are able to inhibit AChE and BuChE. While the GH/CeO2 NPs, treatment in AD induced by AlCl3 inhibited amyloid-ß1-42, substantially enhanced the memory, the cognition coordination of movement in part AD pathogenesis may be alleviated through reducing amyloidogenic pathway and AChE and BuChE activities. The findings of this work provide important comprehension of the chemoprotective activities of iridoids combined with nanoparticles. This could be useful in the development of new therapeutic methods for the treatment of neurodegenerative diseases.

Identification of Riluzole derivatives as novel calmodulin inhibitors with neuroprotective activity by a joint synthesis, biosensor, and computational guided strategy.

The development of new molecules for the treatment of calmodulin related cardiovascular or neurodegenerative diseases is an interesting goal. In this work, we introduce a novel strategy with four main steps: (1) chemical synthesis of target molecules, (2) Förster Resonance Energy Transfer (FRET) biosensor development and in vitro biological assay of new derivatives, (3) Cheminformatics models development and in vivo activity prediction, and (4) Docking studies. This strategy is illustrated with a case study. Firstly, a series of 4-substituted Riluzole derivatives 1-3 were synthetized through a strategy that involves the construction of the 4-bromoriluzole framework and its further functionalization via palladium catalysis or organolithium chemistry. Next, a FRET biosensor for monitoring Ca2+-dependent CaM-ligands interactions has been developed and used for the in vitro assay of Riluzole derivatives. In particular, the best inhibition (80%) was observed for 4-methoxyphenylriluzole 2b. Besides, we trained and validated a new Networks Invariant, Information Fusion, Perturbation Theory, and Machine Learning (NIFPTML) model for predicting probability profiles of in vivo biological activity parameters in different regions of the brain. Next, we used this model to predict the in vivo activity of the compounds experimentally studied in vitro. Last, docking study conducted on Riluzole and its derivatives has provided valuable insights into their binding conformations with the target protein, involving calmodulin and the SK4 channel. This new combined strategy may be useful to reduce assay costs (animals, materials, time, and human resources) in the drug discovery process of calmodulin inhibitors.

Practical Three-Component Regioselective Synthesis of Drug-Like 3-Aryl(or heteroaryl)-5,6-dihydrobenzo[h]cinnolines as Potential Non-Covalent Multi-Targeting Inhibitors To Combat Neurodegenerative Diseases.

Neurodegenerative diseases (NDs) are one of the prominent health challenges facing contemporary society, and many efforts have been made to overcome and (or) control it. In this research paper, we described a practical one-pot two-step three-component reaction between 3,4-dihydronaphthalen-1(2H)-one (1), aryl(or heteroaryl)glyoxal monohydrates (2a-h), and hydrazine monohydrate (NH2NH2•H2O) for the regioselective preparation of some 3-aryl(or heteroaryl)-5,6-dihydrobenzo[h]cinnoline derivatives (3a-h). After synthesis and characterization of the mentioned cinnolines (3a-h), the in silico multi-targeting inhibitory properties of these heterocyclic scaffolds have been investigated upon various Homo sapiens-type enzymes, including hMAO-A, hMAO-B, hAChE, hBChE, hBACE-1, hBACE-2, hNQO-1, hNQO-2, hnNOS, hiNOS, hPARP-1, hPARP-2, hLRRK-2(G2019S), hGSK-3ß, hp38α MAPK, hJNK-3, hOGA, hNMDA receptor, hnSMase-2, hIDO-1, hCOMT, hLIMK-1, hLIMK-2, hRIPK-1, hUCH-L1, hPARK-7, and hDHODH, which have confirmed their functions and roles in the neurodegenerative diseases (NDs), based on molecular docking studies, and the obtained results were compared with a wide range of approved drugs and well-known (with IC50, EC50, etc.) compounds. In addition, in silico ADMET prediction analysis was performed to examine the prospective drug properties of the synthesized heterocyclic compounds (3a-h). The obtained results from the molecular docking studies and ADMET-related data demonstrated that these series of 3-aryl(or heteroaryl)-5,6-dihydrobenzo[h]cinnolines (3a-h), especially hit ones, can really be turned into the potent core of new drugs for the treatment of neurodegenerative diseases (NDs), and/or due to the having some reactionable locations, they are able to have further organic reactions (such as cross-coupling reactions), and expansion of these compounds (for example, with using other types of aryl(or heteroaryl)glyoxal monohydrates) makes a new avenue for designing novel and efficient drugs for this purpose.

Sulfated Polysaccharide-Based Nanocarrier Drives Microenvironment-Mediated Cerebral Neurovascular Remodeling for Ischemic Stroke Treatment.

Stroke is a leading cause of global mortality and severe disability. However, current strategies used for treating ischemic stroke lack specific targeting capabilities, exhibit poor immune escape ability, and have limited drug release control. Herein, we developed an ROS-responsive nanocarrier for targeted delivery of the neuroprotective agent rapamycin (RAPA) to mitigate ischemic brain damage. The nanocarrier consisted of a sulfated chitosan (SCS) polymer core modified with a ROS-responsive boronic ester enveloped by a red blood cell membrane shell incorporating a stroke homing peptide. When encountering high levels of intracellular ROS in ischemic brain tissues, the release of SCS combined with RAPA from nanoparticle disintegration facilitates effective microglia polarization and, in turn, maintains blood-brain barrier integrity, reduces cerebral infarction, and promotes cerebral neurovascular remodeling in a mouse stroke model involving transient middle cerebral artery occlusion (tMCAO). This work offers a promising strategy to treat ischemic stroke therapy.

Leonurus japonicus Houtt. modulates neuronal apoptosis in intracerebral hemorrhage: Insights from network pharmacology and molecular docking.

ETHNOPHARMACOLOGICAL RELEVANCE: Leonurus japonicus Houtt. (Labiatae), commonly known as Chinese motherwort, is a herbaceous flowering plant that is native to Asia. It is widely acknowledged in traditional medicine for its diuretic, hypoglycemic, antiepileptic properties and neuroprotection. Currently, Leonurus japonicus (Leo) is included in the Pharmacopoeia of the People's Republic of China. Traditional Chinese Medicine (TCM) recognizes Leo for its myriad pharmacological attributes, but its efficacy against ICH-induced neuronal apoptosis is unclear. AIMS OF THE STUDY: This study aimed to identify the potential targets and regulatory mechanisms of Leo in alleviating neuronal apoptosis after ICH. MATERIALS AND METHODS: The study employed network pharmacology, UPLC-Q-TOF-MS technique, molecular docking, pharmacodynamic studies, western blotting, and immunofluorescence techniques to explore its potential mechanisms. RESULTS: Leo was found to assist hematoma absorption, thus improving the neurological outlook in an ICH mouse model. Importantly, molecular docking highlighted JAK as Leo's potential therapeutic target in ICH scenarios. Further experimental evidence demonstrated that Leo adjusts JAK1 and STAT1 phosphorylation, curbing Bax while augmenting Bcl-2 expression. CONCLUSION: Leo showcases potential in mitigating neuronal apoptosis post-ICH, predominantly via the JAK/STAT mechanism.

Fragment-based drug discovery and biological evaluation of novel cannabinol-based inhibitors of oxytosis/ferroptosis for neurological disorders.

The oxytosis/ferroptosis regulated cell death pathway is an emerging field of research owing to its pathophysiological relevance to a wide range of neurological disorders, including Alzheimer's and Parkinson's diseases and traumatic brain injury. Developing novel neurotherapeutics to inhibit oxytosis/ferroptosis offers exciting opportunities for the treatment of these and other neurological diseases. Previously, we discovered cannabinol (CBN) as a unique, potent inhibitor of oxytosis/ferroptosis by targeting mitochondria and modulating their function in neuronal cells. To further elucidate which key pharmacophores and chemical space are essential to the beneficial effects of CBN, we herein introduce a fragment-based drug discovery strategy in conjunction with cell-based phenotypic screens using oxytosis/ferroptosis to determine the structure-activity relationship of CBN. The resulting information led to the development of four new CBN analogs, CP1-CP4, that not only preserve the sub-micromolar potency of neuroprotection and mitochondria-modulating activities seen with CBN in neuronal cell models but also have better druglike properties. Moreover, compared to CBN, the analog CP1 shows improved in vivo efficacy in the Drosophila model of mild traumatic brain injury. Together these studies identify the key molecular scaffolds of cannabinoids that contribute to neuroprotection against oxytosis/ferroptosis. They also highlight the advantageous approach of combining in vitro cell-based assays and rapid in vivo studies using Drosophila models for evaluating new therapeutic compounds.

Highly oxidized rearranged derivatives of quinochalcone C-glycosides from Carthamus tinctorius.

Safflopentsides A-C (1-3), three highly oxidized rearranged derivatives of quinochalcone C-glycosides, were isolated from the safflower yellow pigments. Their structures were determined based on a detailed spectroscopic analysis (UV, IR, HR-ESI-MS, 1D and 2D NMR), and the absolute configurations were confirmed by the comparison of experimental ECD spectra with calculated ECD spectra. Compounds 1-3 have an unprecedented cyclopentenone or cyclobutenolide ring A containing C-glucosyl group, respectively. The plausible biosynthetic pathways of compounds have been presented. At 10 µM, 2 showed strong inhibitory activity against rat cerebral cortical neurons damage induced by glutamate and oxygen sugar deprivation.

Fourteen undescribed steroidal saponins from Solanum capsicoides leaves and their neuroprotective effects.

A total of 14 previously undescribed steroidal saponins named capsicsaponins A-N were isolated from the leaves of Solanum capsicoides, encompassing various types, including cholesterol derivatives and pseudospirostanol saponins. The structures of all compounds were determined through comprehensive analysis of spectroscopic data (1D NMR and 2D NMR), along with physicochemical analysis methods (acid hydrolysis, OR, and UV). Moreover, in the H2O2-induced pheochromocytoma cell line model, compounds 1-14 were screened for their neuroprotective effects on cells. The bioassay results demonstrated compounds 8-14 were able to revive cell viability compared to the positive control edaravone. The damage neuroprotection of the most active compound was further explored.