Inhibition of Human Cholinesterases and in†vitro ß-Amyloid Aggregation by Rationally Designed Peptides.

The multifactorial nature of Alzheimer's disease (AD) is now widely recognized, which has increased the interest in compounds that can address more than one AD-associated targets. Herein, we report the inhibitory activity on the human cholinesterases (acetylcholinesterase, hAChE and butyrylcholinesterase, hBChE) and on the AChE-induced ß-amyloid peptide (Aß) aggregation by a series of peptide derivatives designed by mutating aliphatic residues for aromatic ones. We identified peptide W3 (LGWVSKGKLL-NH2 ) as an interesting scaffold for the development of new anti-AD multitarget-directed drugs. It showed the lowest IC50 value against hAChE reported for a peptide (0.99±0.02 µM) and inhibited 94.2 %±1.2 of AChE-induced Aß aggregation at 10 µM. Furthermore, it inhibited hBChE (IC50 , 15.44±0.91 µM), showed no in vivo toxicity in brine shrimp and had shown moderated radical scavenging and Fe2+ chelating capabilities in previous studies. The results are in line with multiple reports showing the utility of the indole moiety for the development of cholinesterase inhibitors.

Amphibian skin extracts as source of bioactive multi-target agents against different pathways of Alzheimer's disease.

Natural products represent a rich source of bioactive compounds that have been historically used to obtain substances with great medicinal potential. The skin of anuran amphibians is a rich source of compounds with a wide range of biological activity. Alzheimer's disease (AD) is a complex disease associated with all kind of different pathways, making their simultaneous modulation necessary. Nowadays anti-AD treatments are focused on enzymatic inhibitors. Here in we report the activity of skin extracts from nine species from Argentina, belonging to three anuran families, as inhibitors of AChE, BChE and MAO-B enzymes. The extracts also showed antioxidant activities, acting as multi-target on four important pathways of AD.

Natural Multi-Target Inhibitors of Cholinesterases and Monoamine Oxidase Enzymes with Antioxidant Potential from Skin Extracts of Hypsiboas cordobae and Pseudis minuta (Anura: Hylidae).

Alzheimer's disease (AD) is the most common cause of dementia, characterized by loss of selective neuronal and normal brain functions. Every year, ten million new cases are diagnosed worldwide. AD is a complex disease associated with all kind of different pathways, making their simultaneous modulation necessary. Nowadays anti-AD treatments are focused on enzymatic inhibitors. The study of the amphibians' skin had acquired great importance in the fields of biology and human health and represents an attractive and novel source for natural compounds with high potential in the development of new drugs. The present work exhibits the power of amphibian skins as a source of bioactive compounds. Herein we report the activity of extracts of two species from Hylidae family (H. cordobae and P. minuta) as reversible inhibitors of acetylcholinesterase and butyrylcholinesterase enzymes. Furthermore, the extracts inhibit MAO-B enzyme and showed antioxidant activities, acting on four important pathways of AD.