Multifunctional nanoparticle-mediated combining therapy for human diseases

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Янв. 1, 2024

Abstract Combining existing drug therapy is essential in developing new therapeutic agents disease prevention and treatment. In preclinical investigations, combined effect of certain known drugs has been well established treating extensive human diseases. Attributed to synergistic effects by targeting various pathways advantages, such as reduced administration dose, decreased toxicity, alleviated resistance, combinatorial treatment now being pursued delivering combat major clinical illnesses, cancer, atherosclerosis, pulmonary hypertension, myocarditis, rheumatoid arthritis, inflammatory bowel disease, metabolic disorders neurodegenerative Combinatorial involves combining or co-delivering two more for a specific disease. Nanoparticle (NP)-mediated delivery systems, i.e., liposomal NPs, polymeric NPs nanocrystals, are great interest wide range due targeted delivery, extended release, higher stability avoid rapid clearance at infected areas. This review summarizes targets diseases, clinically approved combinations the development multifunctional emphasizes strategies based on severe Ultimately, we discuss challenging NP-codelivery translation provide potential approaches address limitations. offers comprehensive overview recent cutting-edge NP-mediated combination

Язык: Английский

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Exploring novel derivatives of isatin-based Schiff bases as multi-target agents: design, synthesis,in vitrobiological evaluation, andin silicoADMET analysis with molecular modeling simulations

RSC Advances, Год журнала: 2023, Номер 13(14), С. 9281 - 9303

Опубликована: Янв. 1, 2023

Recently, scientists developed a powerful strategy called “one drug-multiple targets” to discover vital and unique therapies fight the most challenging diseases.

Язык: Английский

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In-depth investigation of the mechanisms of Schisandra chinensis polysaccharide mitigating Alzheimer's disease rat via gut microbiota and feces metabolomics

International Journal of Biological Macromolecules, Год журнала: 2023, Номер 232, С. 123488 - 123488

Опубликована: Янв. 31, 2023

Язык: Английский

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In vitro enzymatic evaluation of some pyrazolo[1,5‐a]pyrimidine derivatives: Design, synthesis, antioxidant, anti‐diabetic, anti‐Alzheimer, and anti‐arthritic activities with molecular modeling simulation

Drug Development Research, Год журнала: 2022, Номер 84(1), С. 3 - 24

Опубликована: Ноя. 15, 2022

Abstract The strategy of utilizing nitrogen compounds in various biological applications has recently emerged as a powerful approach to exploring novel classes therapeutics face the challenge diseases. A series pyrazolo[1,5‐ ]pyrimidine‐based 3a–l and 5a–f were prepared by direct cyclo‐condensation reaction 5‐amino‐1 H ‐pyrazoles 1a, b with 2‐(arylidene)malononitriles 3‐(dimethylamino)‐1‐aryl‐prop‐2‐en‐1‐ones, respectively. structures new ]pyrimidine confirmed via spectroscopic techniques. vitro activities all ]pyrimidines evaluated assaying total antioxidant capacity, iron‐reducing power, scavenging activity against 1‐diphenyl‐2‐picryl‐hydrazyl (DPPH) 2, 2'‐azinobis‐(3‐ethylbenzothiazoline‐6‐sulfonic acid) (ABTS) radicals, anti‐diabetic, anti‐Alzheimer, anti‐arthritic activities. All displayed good potent bioactivity, three 3g, 3h , 3l most active derivatives. Among these derivatives, compound exhibited highest (total capacity [TAC] = 83.09 mg gallic acid/g; power [IRP] 47.93 µg/ml) free radicals (DPPH 18.77 µg/ml; ABTS 40.44%) compared ascorbic acid 4.28 38.84%). Furthermore, demonstrated strongest inhibition α‐amylase percent 72.91 ± 0.14 acarbose 67.92 0.09%. Similarly, it acetylcholinesterase 62.80 0.06%. However, 3i showed significantly higher percentage for protein denaturation proteinase at 20.66 0.00 26.42 0.06%, Additionally, some silico ADMET properties predicted studied. Finally, molecular docking simulation was performed inside site study their interactions.

Язык: Английский

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Preclinical Models for Alzheimer’s Disease: Past, Present, and Future Approaches

ACS Omega, Год журнала: 2022, Номер 7(51), С. 47504 - 47517

Опубликована: Дек. 13, 2022

A robust preclinical disease model is a primary requirement to understand the underlying mechanisms, signaling pathways, and drug screening for human diseases. Although various models are available several diseases, clinical Alzheimer's (AD) remain underdeveloped inaccurate. The pathophysiology of AD mainly includes presence amyloid plaques neurofibrillary tangles (NFT). Furthermore, neuroinflammation free radical generation also contribute AD. Currently, there wide gap in scientific approaches preventing progression. Most drugs limited symptomatic relief improve deteriorating cognitive functions. To mimic pathogenesis AD, animal like 3XTg-AD 5XFAD primarily used mice therapeutics. Animal include intracerebroventricular-streptozotocin (ICV-STZ), beta-induced, colchicine-induced, etc., focusing on parameters such as decline dementia. Unfortunately, translational rate potential candidates trials poor due limitations imitating pathology models. Therefore, possess modeling. This paper presents an outline that critically assesses applicability current modeling Also, we attempted provide key suggestions best-fit evaluate therapies, which might therapy translation from studies patients with

Язык: Английский

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Development of promising acetylcholinesterase and butyrylcholinesterase inhibitors: Synthesis, in vitro and in silico approaches of pyridine derived fused bis-oxadiazole and bis-thiadiazole derivatives

Journal of Molecular Structure, Год журнала: 2024, Номер 1310, С. 138228 - 138228

Опубликована: Апрель 3, 2024

Язык: Английский

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Neuroprotective effects of dipeptidyl peptidase 4 inhibitor on Alzheimer’s disease: a narrative review

Frontiers in Pharmacology, Год журнала: 2024, Номер 15

Опубликована: Фев. 9, 2024

Insulin resistance in brain and amyloidogenesis are principal pathological features of diabetes-related cognitive decline development Alzheimer’s disease (AD). A growing body evidence suggests that maintaining glucose under control diabetic patients is beneficial for preventing AD development. Dipeptidyl peptidase 4 inhibitors (DDP4is) a class novel glucose-lowering medications through increasing insulin excretion decreasing glucagon levels have shown neuroprotective potential recent studies. This review consolidates extant from earlier new studies investigating the association between DPP4i use, AD, other outcomes. Beyond DPP4i’s benefits alleviating glucose-lowering, underlying mechanisms neuroprotection with were categorized into following sections: (Ferrari et al., Physiol Rev, 2021, 101, 1,047–1,081): DPP4is on directly ameliorating burden β-amyloid plaques reducing formation neurofibrillary tangles; bioactivity DPP4 substrates including glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), stromal-derived factor-1α (SDF-1α) etc.; pleiotropic effects neuronal cells intracerebral structure anti-inflammation, anti-oxidation, anti-apoptosis. We further revisited recently published epidemiological provided supportive data to compliment preclinical evidence. Given there remains lack completed randomized trials aim at assessing effect progression, this expected provide useful insight inhibition as therapeutic target prevention treatment. The helpful informing rationales future clinical research guiding evidence-based practice.

Язык: Английский

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Kaempferol as a potential neuroprotector in Alzheimer's disease

Journal of Food Biochemistry, Год журнала: 2022, Номер 46(12)

Опубликована: Авг. 5, 2022

Alzheimer's disease (AD), the most prevalent neurodegenerative disorder, is largely associated with cognitive disability, amnesia, and abnormal behavior, which accounts for about two third of people dementia worldwide. A growing body research demonstrates that AD connected to several factors, such as aberrant accumulation amyloid-beta (Aβ), increase in hyperphosphorylation Tau protein, formation neurofibrillary tangles, mitochondrial dysfunction, inordinate production reactive oxygen species (ROS). Despite remarkable efforts realize etiology pathophysiology AD, until now, scientists have not developed introduced medications can permanently cease progression AD. Thus, nowadays, on role natural products treatment prevention has attracted great attention. Kaempferol (KMP), one prominent members flavonols, exerts its ameliorative actions via attenuating oxidative stress inflammation, reducing Aβ-induced neurotoxicity, regulating cholinergic system. Therefore, this review article, we outlined possible effects KMP Practical applications (KMP) against The beneficial were addressed both vitro vivo studies; however, conducting further warrant long-term a safe agent. after confirming favorable functions it could be used effective

Язык: Английский

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Carbamate as a potential anti‐Alzheimer's pharmacophore: A review

Drug Development Research, Год журнала: 2023, Номер 84(8), С. 1624 - 1651

Опубликована: Сен. 11, 2023

Alzheimer's disease (AD) is a progressive age-related neurodegenerative brain disorder, which leads to loss of memory and other cognitive dysfunction. The underlying mechanisms AD pathogenesis are very complex still not fully explored. Cholinergic neuronal loss, accumulation amyloid plaque, metal ions dyshomeostasis, tau hyperphosphorylation, oxidative stress, neuroinflammation, mitochondrial dysfunction major hallmarks AD. current treatment options for acetylcholinesterase inhibitors (donepezil, rivastigmine, galantamine) NMDA receptor antagonists (memantine). These FDA-approved drugs mainly provide symptomatic relief without addressing the pathological aspects progression. So, there an urgent need novel drug development that only addresses basic but also shows neuroprotective property. Various research groups across globe working on multifunctional agents amelioration using different core scaffolds their design, carbamate among them. Rivastigmine was first investigated management. fragment, scaffold act as potential inhibitor acetylcholinesterase. In this review, we summarize last 10 years conducted modification with substituents primarily target ChE inhibition, reduce modulate Aβ aggregation.

Язык: Английский

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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

ACS Omega, Год журнала: 2023, Номер 8(10), С. 9394 - 9414

Опубликована: Март 2, 2023

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

Язык: Английский

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