A wide variety of acute and chronic neurodegenerative diseases, including ischemic/traumatic brain injury, Alzheimer's disease, and Parkinson's disease, share common characteristics such as oxidative stress, misfolded proteins, excitotoxicity, inflammation, and neuronal loss. As no drugs are available to prevent the progression of these neurological disorders, intervention strategies using phytochemicals have been proposed as an alternative form of treatment. Among phytochemicals, isothiocyanate sulforaphane, derived from the hydrolysis of the glucosinolate glucoraphanin mainly present in Brassica vegetables, has demonstrated neuroprotective effects in several in vitro and in vivo studies. In particular, evidence suggests that sulforaphane beneficial effects could be mainly ascribed to its peculiar ability to activate the Nrf2/ARE pathway. Therefore, sulforaphane appears to be a promising compound with neuroprotective properties that may play an important role in preventing neurodegeneration.

Alzheimer's disease (AD) is a multifactorial syndrome with several target proteins contributing to its etiology. To confront AD, an innovative strategy is to design single chemical entities able to simultaneously modulate more than one target. Here, we present compounds that inhibit acetylcholinesterase and NMDA receptor activity. Furthermore, these compounds inhibit AChE-induced Abeta aggregation and display antioxidant properties, emerging as lead candidates for treating AD.

One of the characteristics of Alzheimer's disease (AD) that hinders the discovery of effective disease-modifying therapies is the multifactorial nature of its etiopathology. To circumvent this drawback, the use of multi-target-directed ligands (MTDLs) has recently been proposed as a means of simultaneously hitting several targets involved in the development of the AD syndrome. In this paper, a new class of MTDLs based on a polyamine-quinone skeleton, whose lead (memoquin, 2) showed promising properties in preclinical investigations (Cavalli et al. Angew. Chem., Int. Ed. 2007, 46, 3689-3692), is described. 3-29 were tested in vitro against a number of isolated AD-related targets, namely, AChE and BChE, and Abeta aggregation (both AChE-mediated and self-induced). Furthermore, the ability of the compounds to counteract the oxidative stress in a human neuronal-like cellular system (SH-SY5Y cells) was assayed, in both the presence and absence of NQO1, an enzyme able to generate and maintain the reduced form of quinone.

The complex etiology of Alzheimer's disease (AD) prompts scientists to develop multitarget strategies to combat causes and symptoms. We therefore designed, synthesized, and tested new hybrid molecules linking a benzofuran ring to a N-methyl- N-benzylamine through a heptyloxy chain, affording a series of potential multifunctional drugs for AD. The cholinesterase inhibitory activity was extended to the inhibition of Abeta fibril formation for 1, 3, and 5. Compound 3 showed an additional neuroprotective effect.