Imidazole: Multi-targeted Therapeutic Leads for the Management of Alzheimer’s Disease

Abstract

Background: Alzheimer's disease (AD) is a multifactorial disorder coupled with an array of neuropathological mechanisms, including tau phosphorylation, Aβ aggregation, metal ion deregulation, and oxidative stress, along with neuro-inflammation. The clinically available drugs for the management of AD include four acetylcholinesterase inhibitors and one glutamatergic antagonist. These agents provide only temporary relief from the symptoms by altering the neurotransmitter level in the brain. Objective: Keeping in view the focus on research, the numerous pharmacological activities associated with the aromatic diazole heterocyclic nucleus, imidazole, triggered the medicinal chemist to develop a large number of novel anti-AD compounds targeting multiple pathological mechanisms associated with AD. These prepared analogs represent a higher potential against neurological disorders, including AD. This review article aims an ornately pronounce the therapeutic voyage of imidazole and its analogs as anti-AD. Method: It emphasizes the synthesized imidazole derivatives as anti–AD with multiple targets reviewed from the data available on Pubmed. Result: These compounds diminish the pathophysiological aspects of AD; still, further studies are required to prove the safety and efficacy of these compounds in humans. Conclusion: The review aims to provide knowledge and highlight the status of this moiety in the design and development of novel drug candidates against Alzheimer’s disease conditions. Thus, it paves the way for further work.

Imidazoles as Serotonin Receptor Modulators for Treatment of Depression: Structural Insights and Structure–Activity Relationship Studies

“…This can be beneficial for improving the efficacy of molecules [ 181 ]. The development of imidazole-based molecules against various disease states has become a hot topic [ 22 , 42 , 182 , 183 , 184 ]. This moiety can further enter into the development of antidepressants with its enriched structural features.…”

“…The imidazole ring, as a heterocycle, is part of essential amino acids, including histidine (a histamine precursor). It is widely used in drugs such as antifungal agents (ketoconazole, clotrimazole) [ 16 ], antihistamines (cimetidine) [ 15 ], COX-inhibitors [ 17 ], as well as in other diseases (for example, anticancer [ 18 ], antibacterial, antitubercular [ 19 ], anti-inflammatory [ 20 ], antineuropathic [ 21 ], anti-Alzheimer [ 22 , 23 ], antihypertensive [ 24 ], antiviral [ 25 ], anti-obesity [ 26 ], and antiparasitic activity [ 27 ]). Significantly, due to facile structural substituting availability on the imidazole ring, various derived molecules were exploited for gaining potent anticancer activities, for example, topoisomerase inhibitors (as imine-amide imidazole conjugates targeting liver and lung cancer cells) [ 28 ].…”

Schiff’s Base Imidazole Derivatives Synthesis and Evaluation for their Anti-Inflammatory Activity

“…The presence of nitrogen atoms within the imidazole ring imparts unique chemical reactivity and biological activity to these compounds. Schiff bases, derived from the condensation of an imine and an amine, serve as valuable precursors for the synthesis of imidazole derivatives 10 . One of the key mechanisms through which imidazole compounds derived from Schiff bases exert their anti-inflammatory effects is by modulating the activity of enzymes involved in the arachidonic acid metabolism pathway.…”

“…Moreover, imidazole compounds have been reported to interact with various receptors and transcription factors implicated in inflammation. For instance, they may target and modulate the activity of NF-κB signaling, these compounds can downregulate TNF-α and IL-1β 10,[15][16][17] . Additionally, imidazole-based Schiff base derivatives possess antioxidant properties, contributing to their antiinflammatory effects.…”