Pathogenesis of Alzheimer's Disease and Diversity of 1,2,3-Triazole Scaffold in Drug Development: Design Strategies, Structural Insights, and Therapeutic Potential.

Atamjit Singh, Karanvir Singh, Jashandeep Kaur, Ramanpreet Kaur, Aman Sharma, Jasleen Kaur, Uttam Kaur, Renu Chadha, Preet Mohinder Singh Bedi

Journal: ACS chemical neuroscience 2023;14(18):3291-3317

PMID: 37683129

Abstract

Alzheimer's disease is a most prevalent form of dementia all around the globe and currently poses a significant challenge to the healthcare system. Currently available drugs only slow the progression of this disease rather than provide proper containment. Identification of multiple targets responsible for this disease in the last three decades established it as a multifactorial neurodegenerative disorder that needs novel multifunctional agents for its management and the possible reason for the failure of currently available single target clinical drugs. 1,2,3-Triazole is a miraculous nucleus in medicinal chemistry and the first choice for development of multifunctional hybrid molecules. Apart from that, it is an integral component of various drugs in clinical trials as well as in clinical practice. This review is focused on the pathogenesis of Alzheimer's disease and 1,2,3-triazole containing derivatives developed in recent decades as potential anti-Alzheimer's agents. The review will provide (A) precise insight of various established targets of Alzheimer's disease including cholinergic, amyloid, tau, monoamine oxidases, glutamate, calcium, and reactive oxygen species hypothesis and (B) design hypothesis, structure-activity relationships, and pharmacological outcomes of 1,2,3-triazole containing multifunctional anti-Alzheimer's agents. This review will provide a baseline for various research groups working on Alzheimer's drug development in designing potent, safer, and effective multifunctional anti-Alzheimer's candidates of the future.

Address: Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, Punjab 143005, India.; University School of Business, Chandigarh University, Mohali, Punjab 140413, India.; University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India.; Drug and Pollution Testing Laboratory, Guru Nanak Dev University, Amritsar, Punjab 143005, India.

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