In-silico, Synthesis, Characterization, and In-vitro
                    Studies on Benzylidene-based 2-chloroquinolin Derivatives as Free Radical
                    Scavengers in Parkinson’s Disease

Subramanian, Gomathy; Prasad, Kaveri; Chand, Jagdish; Amarjith, Thiyyar K.; Shanish, Antony A.

doi:10.1055/a-2231-1311

Cited by 3 publications

(1 citation statement)

References 36 publications

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“…The Desmond module in the Schrodinger suite 2022 was used to predict the stability of the compound/protein complex and to predict the various conformational changes of the selected compounds in the allosteric active sites of the protein (PDB ID: 4fvt) [21]. The stability study and various interactions between the compound and protein were studied at the time interval of 100 nanoseconds [22]. The parameters such as RMSD, RMSF, and hydrogen bond interactions were studied [23].…”

Section: Molecular Dynamics Studiesmentioning

confidence: 99%

In Silico, Preparation and in Vitro Studies of Benzylidene-Based Hydroxy Benzyl Urea Derivatives as Free Radical Scavengers in Parkinson’s Disease

CHAND,

KANDY,

PRASAD

et al. 2024

Int J App Pharm

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Objective: The study focuses on the benzylidene-based hydroxy benzyl urea derivative as free radical scavengers in PD. Methods: The derivatives were designed, synthesized, and characterized using FTIR, 1H, 13C-NMR, and Mass spectrometry. Further in vitro studies were performed on the SHSY-5Y cell lines. Molecular docking and molecular dynamic studies were performed at 100 ns to predict the binding affinity and stability of the ligand/protein complex. Results: Among the nine derivatives, compounds HBU-2, and HBU-4were found to have the highest binding affinity-9.699 kcal/mol, and-9.020 kcal/mol with the amino acid interactions SER 149, PHE 157, ARG 158, SER 159, ILE 230, and ASP 231. Further, this HBU-1 to HBU-9 derivatives were produced using a synthesis route. The neurotoxicity studies were performed on the SHSY-5Y cells, where the % cell viability for the compound HBU-2, and HBU-4 was 91.22 %, and 90.42 %at a minimal concentration of 125 µg/ml with a p-value<0.011. Further, the cell counts and LDH assay for the compound HBU-2, and HBU-4 with MPP+treatment predicted 0.72-fold change and 0.66-fold change. The ROS % activity was also measured for compounds HBU-2 and HBU-4 in conjunction with the MPP+induction. In the SHSY-5Y cell line, compound HBU-2 downregulated the ROS level to 45%. Conclusion: The synthesized compounds were found to have good free radical scavenging properties on SHSY-5Y neuroblastoma cell lines, considering these derivatives could be further assessed using appropriate PD models.

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Section: Molecular Dynamics Studiesmentioning

confidence: 99%

In Silico, Preparation and in Vitro Studies of Benzylidene-Based Hydroxy Benzyl Urea Derivatives as Free Radical Scavengers in Parkinson’s Disease

CHAND,

KANDY,

PRASAD

et al. 2024

Int J App Pharm

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System biology-based assessment of the molecular mechanism of IMPHY000797 in Parkinson’s disease: a network pharmacology and in-silico evaluation

Subramanian,

Fanai,

Chand

et al. 2024

Sci Rep

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IMPHY000797 derivatives have been well known for their efficacy in various diseases. Moreover, IMPHY000797 derivatives have been found to modulate such genes involved in multiple neurological disorders. Hence, this study seeks to identify such genes and the probable molecular mechanism that could be involved in the pathogenesis of Parkinson’s disease. The study utilized various biological tools such as DisGeNET, STRING, Swiss target predictor, Cytoscape, AutoDock 4.2, Schrodinger suite, ClueGo, and GUSAR. All the reported genes were obtained using DisGeNET, and further, the common genes were incorporated into the STRING to get the KEGG pathway, and all the data was converted to a protein/pathway network via Cytoscape. The clustering of the genes was performed for the gene-enriched data using two-sided hypergeometrics (p-value). The binding affinity of the IMPHY000797 was verified with the highest regulated 25 proteins via utilizing the “Monte Carlo iterated search technique” and the “ Emodel and Glide score ” function. Three thousand five hundred eighty-three genes were identified for Parkinson’s disease and 31 genes for IMPHY000797 compound, among which 25 common genes were identified. Further, the “FOXO-signaling pathway” was identified to be a modulated pathway. Among the 25 proteins, the highest modulated genes and highest binding affinity were exhibited by SIRT3, FOXO1, and PPARGC1A with the compound IMPHY000797. Further, rat toxicity analysis provided the efficacy and safety of the compound. The study was required to identify the probable molecular mechanism, which needs more confirmation from other studies, which is still a significant hit-back. Supplementary Information The online version contains supplementary material available at 10.1038/s41598-024-75603-x.

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Neurotoxicity by Hypoxia an Intermediate Between Alpha-synuclein and Mitochondrial Dysfunction in Parkinson’s Disease

Chand,

Fanai,

Antony

et al. 2024

Journal of Pharmacology and Pharmacotherapeutics

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This review article explores the relationship between alpha-synuclein and mitochondrial dysfunction in Parkinson’s disease (PD), focusing on the role of hypoxia as an intermediate factor. The interaction between alpha-synuclein and mitochondria, particularly through membranal lipids such as cardiolipins, is highlighted as a key factor in mitochondrial disruption and neurodegeneration. Hypoxia, caused by oxygen deprivation, is identified as a crucial link between alpha-synuclein and mitochondrial regulation, leading to neuronal death in PD. The article also discusses the involvement of other proteins, such as peroxisome proliferator-activated receptor gamma coactivator, Sirtuin-1, Sirtuin-3 and adenosine monophosphate-activated protein kinase, in maintaining mitochondrial biogenesis during hypoxia. The study emphasizes the need for further research to understand the complex molecular interactions causing Lewy body aggregation, improper mitochondrial functioning and neurodegeneration in PD, with a specific focus on the role of hypoxia. Alpha-synuclein aggregation disrupts mitochondrial respiration, leading to mitochondrial dysfunction and increased production of reactive oxygen species. Mitochondrial dysfunction, in turn, causes neurodegeneration in PD. Oligomeric alpha-synuclein results in mitochondrial dysfunction, lethal synaptic disruption and reduced adenosine triphosphate generation. Oligomeric alpha-synuclein also increases the accumulation of mitochondrial rho nucleotide guanosine triphosphate, leading to delayed mitophagy. Hypoxia, another factor in PD, alters both alpha-synuclein and mitochondria. Controlling hypoxia reduces the oligomerization of alpha-synuclein. The interaction between alpha-synuclein and mitochondria is complex, and determining the primary player in inducing the other is still debatable.

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In-silico, Synthesis, Characterization, and In-vitro Studies on Benzylidene-based 2-chloroquinolin Derivatives as Free Radical Scavengers in Parkinson’s Disease

Cited by 3 publications

References 36 publications

In Silico, Preparation and in Vitro Studies of Benzylidene-Based Hydroxy Benzyl Urea Derivatives as Free Radical Scavengers in Parkinson’s Disease

In Silico, Preparation and in Vitro Studies of Benzylidene-Based Hydroxy Benzyl Urea Derivatives as Free Radical Scavengers in Parkinson’s Disease

System biology-based assessment of the molecular mechanism of IMPHY000797 in Parkinson’s disease: a network pharmacology and in-silico evaluation

Neurotoxicity by Hypoxia an Intermediate Between Alpha-synuclein and Mitochondrial Dysfunction in Parkinson’s Disease

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