A new naphthalene derivative with anti-amyloidogenic activity as potential therapeutic agent for Alzheimer's disease

Rivera-Marrero, Suchitil; Bencomo-Martínez, Alberto; Salazar, Erika Orta; Sablón-Carrazana, Marquiza; García-Pupo, Laura; Zoppolo, Florencia; Arredondo, Florencia; Dapueto, Rosina; Santi, María Daniela; Kreimerman, Ingrid; Pardo, Tania; Reyes, Laura; Galán, Lı́dice; León-Chaviano, Samila; Espinosa-Rodríguez, Luis A.; Valle, Roberto Menéndez-Soto del; Savio, Eduardo; Cintra, Sofía Díaz; Rodríguez-Tanty, Chryslaine

doi:10.1016/j.bmc.2020.115700

Cited by 9 publications

(6 citation statements)

References 82 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…L-dopa has been exerting potential activity by reloading dopamine quantity in striatum of brain by decarboxylation of enzymes in synaptic neurons. 29 Here we used rat animal model with induced 6-OHDA. Where 6-OHDA lesion eliminated most of the dopamine receptors in the nigra part of brain leading to loss of dopamine levels in brain.…”

Section: In Vivo Studymentioning

confidence: 99%

Synthesis and Biological Evaluation of the Selected Naphthalene Substituted Azetidinone Derivatives Targeting Parkinson’s Disease

Subramanian¹,

Chand²,

Jupudi³

et al. 2023

Ind. J. Pharm. Edu. Res.

View full text Add to dashboard Cite

Aim/Background: Parkinson's Disease (PD), the loss of dopaminergic neurons in the substantial nigra part of the brain leading to neurodegeneration. Materials and Methods: The objective of this study was to observe the neuroprotective effect of the synthesized derivatives in 6-hydroxydopamine (6-OHDA) induced rat model. Here, designed naphthalene substituted azetidinone compounds defended the lesions caused by 6-OHDA in rat model for PD. Male wistar rats (250g) were subjected into sham operated, controlled 6-OHDA, 6-OHDA treated L-dopa (Levodopa) and lesioned 6-OHDA with azetidinone derivatives (30mg/kg) where oxidative stress and behavioral characteristic were observed. Results: Induced synthesized derivatives partly have shown the reversed behavioral and neuronal changes compared to 6-OHDA lesioned rats. The free radical scavenging activity for the compound IVc, IVe and IVf were found to be 88, 70, 78 respectively as compared to that of 6-OHDA with L-dopa with 90%. Conclusion: The efficacy of the azetidinone derivatives was found to be promising in providing relief to oxidative stress and the derivatives could be used in the therapeutic approaches in preventing neurodegeneration.

show abstract

Section: In Vivo Studymentioning

confidence: 99%

Synthesis and Biological Evaluation of the Selected Naphthalene Substituted Azetidinone Derivatives Targeting Parkinson’s Disease

Subramanian¹,

Chand²,

Jupudi³

et al. 2023

Ind. J. Pharm. Edu. Res.

View full text Add to dashboard Cite

show abstract

“…Furthermore, it provides the coordinates for the whole range of amino acids, i.e., 1–42, and so serves as one of the most relevant target structures for structure-based computational study. Certain studies included only pentamer units of protofibrils and so ignored the sites in the interfacial region. − Here we include the entire protofibril, and so the molecular docking algorithm could locate binding sites on the surface, in the core, and in the interfacial region (see Figure ). As the binding site details for DANIR-2c are not available, we performed a blind docking by including the entire fibril within the grid box.…”

Section: Computational Detailsmentioning

confidence: 99%

Computational Investigations into Two-Photon Fibril Imaging Using the DANIR-2c Probe

Murugan

Zaleśny

2023

J. Phys. Chem. B

View full text Add to dashboard Cite

The design of novel fibril imaging molecules for medical diagnosis requires the simultaneous optimization of fibril-specific optical properties and binding specificity toward amyloid fibrils. Because of the possibility to monitor internal organs and deep tissues, the two-photon probes that can absorb in the infrared (IR) and near-IR (NIR) region with a significant two-photon absorption cross section are of immense interest. To contribute to this exploration of chemical compounds suitable for two-photon fibril imaging, we have computationally studied the one- and two-photon properties of a donor–acceptor-substituted DANIR-2c probe, which was used for in vivo detection of β-amyloid deposits using fluorescence spectroscopy. In particular, a multiscale computational approach was employed involving molecular docking, molecular dynamics, hybrid QM/MM molecular dynamics, and coupled-cluster/MM to study the binding of the studied probe to amyloid fibril and its one- and two-photon absorption properties in the fibrillar environment. Multiple binding sites are available for this probe in amyloid fibril, and the one corresponding to the largest binding affinity exhibits also the largest and experimentally meaningful two-photon absorption cross section, thus demonstrating the potential of the studied probe in two-photon microscopy.

show abstract

“…However, a precise etiology is still elusive. 19 Several hypotheses govern AD progression, among which cholinergic transmission dysfunction and formation of Aβ-aggregates have emerged as the widely acceptable pathophysiology for synaptic loss and neurodegeneration. 20,21 The cholinesterase enzymes (ChEs), i.e., AChE and butyrylcholine esterase (BChE) inhibitors, are the most promising therapeutic strategy to halt proteolytic degradation of the ACh into choline and acetic acid and increase ACh levels in synaptic cleft to regulate cholinergic neurotransmission.…”

Section: Introductionmentioning

confidence: 99%

“…Several mechanisms and hypotheses have been proposed explaining the progression of AD. However, a precise etiology is still elusive . Several hypotheses govern AD progression, among which cholinergic transmission dysfunction and formation of Aβ-aggregates have emerged as the widely acceptable pathophysiology for synaptic loss and neurodegeneration. , The cholinesterase enzymes (ChEs), i.e.…”

Section: Introductionmentioning

confidence: 99%

Development and Evaluation of Some Molecular Hybrids of N-(1-Benzylpiperidin-4-yl)-2-((5-phenyl-1,3,4-oxadiazol-2-yl)thio) as Multifunctional Agents to Combat Alzheimer’s Disease

et al. 2023

View full text Add to dashboard Cite

A series of some novel compounds (SD-1−17) were designed following a molecular hybridization approach, synthesized, and biologically tested for hAChE, hBChE, hBACE-1, and Aβ aggregation inhibition potential to improve cognition and memory functions associated with Alzheimer's disease. Compounds SD-4 and SD-6 have shown multifunctional inhibitory profiles against hAChE, hBChE, and hBACE-1 enzymes in vitro. Compounds SD-4 and SD-6 have also shown anti-Aβ aggregation potential in self-and acetylcholinesterase (AChE)-induced thioflavin T assay. Both compounds have shown a significant propidium iodide (PI) displacement from the cholinesterase-peripheral active site (ChE-PAS) region with excellent blood−brain barrier (BBB) permeability and devoid of neurotoxic liabilities. Compound SD-6 ameliorates cognition and memory functions in scopolamine-and Aβ-induced behavioral rat models of Alzheimer's disease (AD). Ex vivo biochemical estimation revealed a significant decrease in malonaldehyde (MDA) and AChE levels, while a substantial increase of superoxide dismutase (SOD), catalase, glutathione (GSH), and ACh levels is seen in the hippocampal brain homogenates. The histopathological examination of brain slices also revealed no sign of neuronal or any tissue damage in the SD-6treated experimental animals. The in silico molecular docking results of compounds SD-4 and SD-6 showed their binding with hChE-catalytic anionic site (CAS), PAS, and the catalytic dyad residues of the hBACE-1 enzymes. A 100 ns molecular dynamic simulation study of both compounds with ChE and hBACE-1 enzymes also confirmed the ligand−protein complex's stability, while quikprop analysis suggested drug-like properties of the compounds.

show abstract

A new naphthalene derivative with anti-amyloidogenic activity as potential therapeutic agent for Alzheimer's disease

Cited by 9 publications

References 82 publications

Synthesis and Biological Evaluation of the Selected Naphthalene Substituted Azetidinone Derivatives Targeting Parkinson’s Disease

Synthesis and Biological Evaluation of the Selected Naphthalene Substituted Azetidinone Derivatives Targeting Parkinson’s Disease

Computational Investigations into Two-Photon Fibril Imaging Using the DANIR-2c Probe

Development and Evaluation of Some Molecular Hybrids of N-(1-Benzylpiperidin-4-yl)-2-((5-phenyl-1,3,4-oxadiazol-2-yl)thio) as Multifunctional Agents to Combat Alzheimer’s Disease

Contact Info

Product

Resources

About