Insights into (S)-rivastigmine inhibition of butyrylcholinesterase (BuChE): Molecular docking and saturation transfer difference NMR (STD-NMR)

Rivastigmine is a very important drug prescribed for the treatment of Alzheimer's disease (AD) symptoms. It is a dual inhibitor, in that it inhibits both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). For our screening program on the discovery of new rivastigmine analogue hits for human butyrylcholinesterase (hBuChE) inhibition, we investigated the interaction of this inhibitor with BuChE using the complimentary approach of the biophysical method, saturation transfer difference (STD)-NMR and molecular docking. This allowed us to obtain essential information on the key binding interactions between the inhibitor and the enzyme to be used for screening of hit compounds. The main conclusions obtained from this integrated study was that the most dominant interactions were (a) H-bonding between the carbamate carbonyl of the inhibitor and the NH group of the imidazole unit of H434, (b) stacking of the aromatic unit of the inhibitor and the W82 aromatic unit in the choline binding pocket via pi-pi interactions and (c) possible CH/pi interactions between the benzylic methyl group and the N-methyl groups of the inhibitor and W82 of the enzyme.

Self-care in older people with functional deficit: needs of long-term care.

The group of 65-year-olds is becoming more numerous and with greater needs for health care. So, is necessary the reflection about new models of provision, organization, and allocation of health resources. According to the United Nations Organization, 2015, in 2050 elderly people will reach two million people (20% of the world’s population), what mean that the number of people over 60 years old will exceed a population of young people under 15 years. Parallel to aging, less healthy lifestyles have contributed to the prevalence of chronic diseases, especially cerebrovascular diseases. Hypertension and diabetes mellitus are risk factors and increase predisposition to other diseases. With aging, there is an increased risk for developing chronic, oncological and degenerative diseases, which account for more than 50% of the burden of diseases, with profound implications on independency, use of health care and services.