Molecular Targets of Bis (7)-Cognitin and Its Relevance in Neurological Disorders: A Systematic Review

Abstract

Background: The exact mechanisms involved in the pathogenesis of neurodegenerative conditions are not fully known. The design of drugs that act on multiple targets represents a promising approach that should be explored for more effective clinical options for neurodegenerative disorders. B7C is s synthetic drug that has been studied for over 20 years and represents a promising multi-target drug for the treatment of neurodegenerative disorders, such as AD. Aims: The present systematic review, thus, aims at examining existing studies on the effect of B7C on different molecular targets and at discussing the relevance of B7C in neurological disorders. Methods: A list of predefined search terms was used to retrieve relevant articles from the databases of Embase, Pubmed, Scopus, and Web of Science. The selection of articles was done by two independent authors, who were considering articles concerned primarily with the evaluation of the effect of B7C on neurological disorders. Only full-text articles written in English were included; whereas, systematic reviews, meta-analyses, book chapters, conference subtracts, and computational studies were excluded. Results: A total of 2,266 articles were retrieved out of which 41 articles were included in the present systematic review. The effect of B7C on molecular targets, including AChE, BChE, BACE-1, NMDA receptor, GABA receptor, NOS, and Kv4.2 potassium channels was evaluated. Moreover, the studies that were included assessed the effect of B7C on biological processes, such as apoptosis, neuritogenesis, and amyloid beta aggregation. The animal studies examined in the review focused on the effect of B7C on cognition and memory. Conclusions: The beneficial effects observed on different molecular targets and biological processes relevant to neurological conditions confirm that B7C is a promising multi-target drug with the potential to treat neurological disorders.

Structural Modification, In Vitro, In Vivo, Ex Vivo, and In Silico Exploration of Pyrimidine and Pyrrolidine Cores for Targeting Enzymes Associated with Neuroinflammation and Cholinergic Deficit in Alzheimer’s Disease

“…However, it is still considered a classical pharmacophore for structural modification and design of new multitarget inhibitors to treat AD. Later on, bis (7)-tacrine ( 2 , Figure ), a structure–activity relationship (SAR) outcome of a dimer of total hip arthroplasty (THA) with a spacer length of seven methylene units, also attracted the attention of AD researchers due to its blood–brain barrier (BBB) permeability and high lipophilic profile …”

In Search of a Function for the N6-Methyladenosine in Epitranscriptome, Autophagy and Neurodegenerative Diseases

“…For example, AD is determined by the increase in pathologic amyloid, and eventually directs to dementia, whereas PD is determined by the loss of dopaminergic neurons, and primarily directs to several extrapyramidal symptoms. As aberrant autophagy has been observed in neurodegenerative diseases, including AD, PD, HD, and/or amyotrophic lateral sclerosis (ALS) [ 86 ], something to modify the autophagy might contribute to the development of treatment for these neurodegenerative diseases. In this regard, as gut microbiota can play an imperative role in the response of inflammation, autophagy, oxidative stress, and/or cellular apoptosis, even for organs distant from the gut such as the kidney and/or brain [ 87 , 88 ], the gut microbiota might contribute to improve the pathology of neurodegenerative diseases.…”

Bis-Amiridines as Acetylcholinesterase and Butyrylcholinesterase Inhibitors: N-Functionalization Determines the Multitarget Anti-Alzheimer’s Activity Profile

“…As a result, B7C is one of the most effective AChE inhibitors, as well as a potent blocker of AChE-induced β-amyloid aggregation. Additionally, B7C was found to be an inhibitor of β-amyloid self-aggregation, a noncompetitive antagonist of NMDA receptors that can prevent glutamate-induced damage to hippocampal neurons, an antagonist of a GABA A receptor, and an inhibitor of the nitric oxide synthase signaling pathway [ 69 ]. Thus, in contrast to its parent compound tacrine, B7C is a multi-target compound that shows promising biological activity.…”