A comprehensive review on the progress and challenges of tetrahydroisoquinoline derivatives as a promising therapeutic agent to treat Alzheimer's disease

Abstract

Alzheimer's disease (AD) is the most common and irreversible neurodegenerative disorder worldwide. While the precise mechanism behind this rapid progression and multifaceted disease remains unknown, the numerous drawbacks of the available therapies are prevalent, necessitating effective alternative treatment methods. In view of the rising demand for effective AD treatment, numerous reports have shown that tetrahydroisoquinoline (THIQ) is a valuable scaffold in various clinical medicinal molecules and has a promising potential as a therapeutic agent in treating AD due to its significant neuroprotective, anti-inflammatory, and antioxidative properties via several mechanisms that target the altered signaling pathways. Therefore, this review comprehensively outlines the potential application of THIQ derivatives in AD treatment and the challenges in imparting the action of these prospective therapeutic agents. The review emphasizes a number of THIQ derivatives, including Dauricine, jatrorrhizine, 1MeTIQ, and THICAPA, that have been incorporated in AD studies in recent years. Subsequently, a dedicated section of the review briefly discusses the emerging potential benefits of multi-target therapeutics, which lie in their ability to be integrated with alternative therapeutics. Eventually, this review elaborates on the rising challenges and future recommendations for the development of therapeutic drug agents to treat AD effectively. In essence, the valuable research insights of THIQ derivatives presented in this comprehensive review would serve as an integral reference for future studies to develop potent therapeutic drugs for AD research.

Keywords: Alzheimer's disease; Multi-target therapeutics approach; Neuroprotection; Tetrahydroisoquinoline; Therapeutic agent.

Fig. 1

Chemical structure of a naturally occurring THIQ.

Fig. 2

Comprehensive pathway of THIQ derivatives through various mechanisms of action within the neuron in AD research. The pink background represents the intracellular environment, and the blue background represents the extracellular compartment of the neuron. The mechanism of the respective THIQ derivatives is labeled with numbers: (1) Dauricine, (2) 1MeTIQ, (3) Jatrorrhizine, and (4) THICAPA. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)