Design and synthesis of H2S-donor hybrids: A new treatment for Alzheimer's disease?

Design and synthesis of H2S-donor hybrids: A new treatment for Alzheimer's disease? Eur J Med Chem. 2019 Sep 27;184:111745 Authors: Sestito S, Pruccoli L, Runfola M, Citi V, Martelli A, Saccomanni G, Calderone V, Tarozzi A, Rapposelli S Abstract Hydrogen sulphide (H2S) is an endogenous gasotransmitter, largely known as a pleiotropic mediator endowed with antioxidant, anti-inflammatory, pro-autophagic, and neuroprotective properties. Moreover, a strong relationship between H2S and aging has been recently identified and consistently, a significant decline of H2S levels has been observed in patients affected by Alzheimer's disease (AD). On this basis, the use of H2S-donors could represent an exciting and intriguing strategy to be pursued for the treatment of neurodegenerative diseases (NDDs). In this work, we designed a small series of multitarget molecules combining the rivastigmine-scaffold, a well-established drug already approved for AD, with sulforaphane (SFN) and erucin (ERN), two natural products deriving from the enzymatic hydrolysis of glucosinolates contained in broccoli and rocket, respectively, endowed both with antioxidant and neuroprotective effects. Notably, all new synthetized hybrids exhibit a H2S-donor profile in vitro and elicit protective effects in a model of LPS-induced microglia inflammation. Moreover, a decrease in NO production has been observed in LPS-stimulated cells pre-treated with the compounds. Finally, t...
Source: European Journal of Medicinal Chemistry - Category: Chemistry Authors: Tags: Eur J Med Chem Source Type: research