Evaluation of γ-carboline-phenothiazine conjugates as simultaneous NMDA receptor blockers and cholinesterase inhibitors

Schwarthoff, Sigrid; Tischer, Nicolas; Sager, Henrike; Schätz, Bianca; Rohrbach, Marius M.; Raztsou, Ihar; Robaa, Dina; Gaube, Friedemann; Arndt, Hans‐Dieter; Winckler, Thomas

doi:10.1016/j.bmc.2021.116355

Cited by 9 publications

(2 citation statements)

References 29 publications

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“…Neurotransmitters and their signaling are impaired in patients with AD [ 52 ]. AD is associated with cognitive dysfunctions such as memory loss caused by progressive deficits in cholinergic and glutamate signaling in the central nervous system [ 53 ]. Cognitive deficits are associated with the degeneration of cholinergic neurons [ 54 ], and the lack of the cholinergic system is believed to play a crucial role in cognitive impairment [ 55 ].…”

Section: Ad Relation To the Cholinergic Systemmentioning

confidence: 99%

Role of Cholinergic Signaling in Alzheimer’s Disease

et al. 2022

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Acetylcholine, a neurotransmitter secreted by cholinergic neurons, is involved in signal transduction related to memory and learning ability. Alzheimer’s disease (AD), a progressive and commonly diagnosed neurodegenerative disease, is characterized by memory and cognitive decline and behavioral disorders. The pathogenesis of AD is complex and remains unclear, being affected by various factors. The cholinergic hypothesis is the earliest theory about the pathogenesis of AD. Cholinergic atrophy and cognitive decline are accelerated in age-related neurodegenerative diseases such as AD. In addition, abnormal central cholinergic changes can also induce abnormal phosphorylation of ttau protein, nerve cell inflammation, cell apoptosis, and other pathological phenomena, but the exact mechanism of action is still unclear. Due to the complex and unclear pathogenesis, effective methods to prevent and treat AD are unavailable, and research to explore novel therapeutic drugs is various and active in the world. This review summaries the role of cholinergic signaling and the correlation between the cholinergic signaling pathway with other risk factors in AD and provides the latest research about the efficient therapeutic drugs and treatment of AD.

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Section: Ad Relation To the Cholinergic Systemmentioning

confidence: 99%

Role of Cholinergic Signaling in Alzheimer’s Disease

et al. 2022

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“…Intermediate 9 was synthesized from commercial available 4-methoxyphenylhydrazine hydrochloride 7 and piperidone derivative 8 via Fischer indole synthesis process according to the reported methods in a high yield. [29][30][31] The oxidation of compound 9 with Pd/C gave γ-carboline derivative 10 in an excellent yield, [32] which reacted with different chlorides and alkyl halides in the presence of corresponding bases to deliver the desired products 11a～ 11o and 12a～12k in moderate to high yields, respectively (Table 1). Moreover, stirring the key synthon 10 with var- ious haloalkanes heating in acetonitrile afforded the ammonium salts 13a～13t in moderate to high yields (Table 1).…”

Section: Resultsmentioning

confidence: 99%

Novel γ-Carboline Derivatives as Antibacterial Agents: Synthesis and Antibacterial Evaluation

Huo,

Li,

Wang

et al. 2024

Chinese Journal of Organic Chemistry

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Carboline Regioisomers Based on Unified Synthetic Approaches

Arshad

Mordi

2023

Adv Synth Catal

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Carbolines are a prominent class of tricyclic alkaloids omnipresent in natural products and bioactive compounds. Four different carboline regioisomers are known (α-, β-, γ-, and δ-carbolines), which can be classified according to the nitrogen atom position inside the pyridine ring. As an emerging structural motif in drug discovery, a multitude of synthetic methods have been established for the construction of carboline frameworks, which in general requires customized approaches for the assembly of each regioisomer. Distinguishingly, their frameworks are also accessible from unified approaches, which are capable of generating multiple regioisomers, thus suitable for introducing diversity in isomeric carbolines. In this review, the construction of isomeric carbolines based on unified synthetic approaches is summarized.

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Evaluation of γ-carboline-phenothiazine conjugates as simultaneous NMDA receptor blockers and cholinesterase inhibitors

Cited by 9 publications

References 29 publications

Role of Cholinergic Signaling in Alzheimer’s Disease

Role of Cholinergic Signaling in Alzheimer’s Disease

Novel γ-Carboline Derivatives as Antibacterial Agents: Synthesis and Antibacterial Evaluation

Carboline Regioisomers Based on Unified Synthetic Approaches

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