Abstract
Alzheimer’s disease (AD) is a complex neurodegenerative disorder with a multifaceted pathogenesis. This fact has long halted the development of effective anti-AD drugs. Recently, a therapeutic strategy based on the exploitation of Brazilian biodiversity was set with the aim of discovering new disease-modifying and safe drugs for AD. In this review, we will illustrate our efforts in developing new molecules derived from Brazilian cashew nut shell liquid (CNSL), a natural oil and a byproduct of cashew nut food processing, with a high content of phenolic lipids. The rational modification of their structures has emerged as a successful medicinal chemistry approach to the development of novel anti-AD lead candidates. The biological profile of the newly developed CNSL derivatives towards validated AD targets will be discussed together with the role of these molecular targets in the context of AD pathogenesis.
Highlights
Dementia is a major public health concern, amplified by a fast-growing older population
As long as a cure remains elusive, Alzheimer’s disease (AD) stands as a dramatic unmet clinical need and a most challenging and pressing therapeutic area, so as scientists, we should do everything possible to solve the problem, and pursue any drug discovery approach founded on solid hypotheses [6]
Motivated by the above results, we considered cardanols 15b–d as suitable frameworks for the design of AChE inhibitors with higher potency
Summary
Dementia is a major public health concern, amplified by a fast-growing older population. As long as a cure remains elusive, AD stands as a dramatic unmet clinical need and a most challenging and pressing therapeutic area, so as scientists, we should do everything possible to solve the problem, and pursue any drug discovery approach founded on solid hypotheses [6] One of such approach is the use of natural products. In addition to an anti-amyloid activity, GV-971 is reported to beneficially modulate gut microbiota, reduce metabolite-driven peripheral infiltration of immune cells into the brain, and inhibit neuroinflammation [11] These success stories, together with the general notion that natural products have an intrinsic multi-target mechanism of action [12]. Beforehand, an overview of the role of these molecular targets in the context of AD pathogenesis will be discussed
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