Dual targeting of acetylcholinesterase and tau aggregation: Design, synthesis and evaluation of multifunctional deoxyvasicinone analogues for Alzheimer’s disease

Manzoor, Shoaib; Gabr, Moustafa T.; Rasool, Bisma; Pal, Kavita; Hoda, Nasimul

doi:10.1016/j.bioorg.2021.105354

Cited by 19 publications

(19 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[28] When the literature is examined the inhibition of both enzymes by similar molecules designed and synthesized by our previous studies led us to carry out this study. [16,29] The aim of this study was to investigate the inhibition effects of novel synthesized nitrogen-based novel heterocyclic compounds (1-13) on acetylcholinesterase as cholinergic enzyme and α-glycosidase as digestive enzyme. Also, their inhibition profiles and molecular docking were compared to the standard compounds like Tacrine and Acarbose as clinical inhibitors for AD and T2DM diseases.…”

Section: Chemistryselectmentioning

confidence: 99%

“…AD is characterized by multiple cognitive impairments such as memory loss and difficulties in learning and thinking [15] . It is the most prominent form of dementia and is characterized by progressive deterioration in memory skills and functions [16] . It has been reported that the changes in AChE and BChE activities in the hippocampus and cerebral cortex contribute to the progression of AD disease.…”

Section: Introductionmentioning

confidence: 99%

“…So, there is strong demand to find and synthesize novel AGIs with less toxicity and side effects [28] . When the literature is examined the inhibition of both enzymes by similar molecules designed and synthesized by our previous studies led us to carry out this study [16,29] …”

Section: Introductionmentioning

confidence: 99%

“…[15] It is the most prominent form of dementia and is characterized by progressive deterioration in memory skills and functions. [16] It has been reported that the changes in AChE and BChE activities in the hippocampus and cerebral cortex contribute to the progression of AD disease. Unchanged or increased BChE activity and decreased AChE activity are commonly observed in certain regions of brain of patients suffering from AD.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Synthesis, Characterization, Molecular Docking, Acetylcholinesterase and α‐Glycosidase Inhibition Profiles of Nitrogen‐Based Novel Heterocyclic Compounds

et al. 2022

View full text Add to dashboard Cite

In this study, a series of nitrogen-based novel heterocyclic compounds were synthesized and characterized by elemental analysis, IR and NMR spectra. The novel synthesized nitrogenbased novel heterocyclic compounds were evaluated against the acetylcholinesterase (AChE) and α-glycosidase enzymes. These compounds showed IC 50 values in range of 0.76-28.04 μM against AChE as a cholinergic enzyme, and 26.10-82.17 μM against α-glycosidase as a hydrolytic enzyme. On the other hand, they demonstrated K i values between 1.25 � 0.22-25.36 � 4.72 μM against AChE, and 25.07 � 4.57-78.55 � 17.04 μM against α-glycosidase enzymes. The synthesized nitrogen-based novel heterocyclic compounds exhibited effective inhibition profiles against both indicated metabolic enzymes. These results may contribute to the development of new drugs particularly to treat some disorders, which widespread display in the world including Alzheimer's disease and diabetes. Furthermore, molecular docking calculations were made to compare the theoretical biological activities of nitrogen-based novel heterocyclic compounds against proteins including enzymes. After these calculations, ADME/T analysis was performed to examine the drug properties of nitrogenbased novel heterocyclic compounds.

show abstract

Section: Chemistryselectmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Synthesis, Characterization, Molecular Docking, Acetylcholinesterase and α‐Glycosidase Inhibition Profiles of Nitrogen‐Based Novel Heterocyclic Compounds

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Clinically, A β is one of the prominent pathological cause involved in the progression of AD [20,21] leading to neurofibrillary tangles, senile plaques, dementia, and neuron death [22–24] . Hence, designing inhibitors addressing amyloid aggregation is one of the promising approaches to inhibit A β accumulation and toxicity in AD brains [25,26] .…”

Section: Introductionmentioning

confidence: 99%

Pharmacological Investigations of Selected Multitarget‐Direct Ligands for the Treatment of Alzheimer's Disease

et al. 2022

Self Cite

View full text Add to dashboard Cite

Alzheimer's disease (AD) is a complex, degenerative condition linked to memory loss and cognitive degradation. The phenyl sulfonyl-pyrimidine derivatives containing dimethoxy-chloro substituent (BS-10 and BS-22) were previously recognized as multitarget-directed ligands (MTDLs) due to their ability to inhibit acetylcholinesterase (AChE) at low nanomolar concentrations (IC 50 = 47.33 � 0.02 and 51.36 � 0.04 nM respectively) while also reducing amyloid beta (Aβ) aggregation. In the current investigation, we investigated the in vivo and ex-vivo effects of BS-10 and BS-22 chemicals on cognition and the cholinergic system. We have used scopolamine and Aβ 1-42 models of cognitive impairment which were measured during Y-maze and passive avoidance apparatus. Results showed that BS-10 at 10 mg/kg compared to BS-22 at 20 mg/kg rescued memory impairment more significantly. Moreover, ex-vivo and biochemical studies exhibited both compounds improved the hippocampal acetylcholine (Ach) level by reducing AChE activity as well as antioxidant properties. In addition, BS-10 and BS-22 attenuated Aβ 1-42 induced cognitive deficiency in rats during Y-maze tests and significantly restored mitochondrial membrane potential and reduced the tau protein level in rats (p < 0.05). In summary, our results indicated that MTDLs BS-10 and BS-22 would be a promising therapeutic approach in AD.

show abstract

Insights into the chemistry and therapeutic potential of acrylonitrile derivatives

Tan

Zengin

2021

Archiv der Pharmazie

View full text Add to dashboard Cite

Acrylonitrile is a fascinating scaffold widely found in many natural products, drugs, and drug candidates with various biological activities. Several drug molecules such as entacapone, rilpivirine, teriflunomide, and so forth, bearing an acrylonitrile moiety have been marketed. In this review, diverse synthetic strategies for constructing desired acrylonitriles are discussed, and the different biological activities and medicinal significance of various acrylonitrile derivatives are critically evaluated. The information gathered is expected to provide rational guidance for the development of clinically useful agents from acrylonitriles.

show abstract

Dual targeting of acetylcholinesterase and tau aggregation: Design, synthesis and evaluation of multifunctional deoxyvasicinone analogues for Alzheimer’s disease

Cited by 19 publications

References 65 publications

Synthesis, Characterization, Molecular Docking, Acetylcholinesterase and α‐Glycosidase Inhibition Profiles of Nitrogen‐Based Novel Heterocyclic Compounds

Synthesis, Characterization, Molecular Docking, Acetylcholinesterase and α‐Glycosidase Inhibition Profiles of Nitrogen‐Based Novel Heterocyclic Compounds

Pharmacological Investigations of Selected Multitarget‐Direct Ligands for the Treatment of Alzheimer's Disease

Insights into the chemistry and therapeutic potential of acrylonitrile derivatives

Contact Info

Product

Resources

About