In silico Structure-based Identification of Novel Acetylcholinesterase Inhibitors Against Alzheimer's Disease.

OBJECTIVE AND BACKGROUND: Inhibition of acetylcholinesterase (AChE) has gained much importance since the discovery of the involvement of peripheral anionic site as an allosteric regulator of AChE. Characterized by the formation of ß-amyloid plaques, Alzheimer's disease (AD) is currently one of the leading causes of death across the world. Progression in this neurodegenerative disorder causes deficit in the cholinergic activity that leads towards cognitive decline. Therapeutic interventions in AD are largely focused upon AChE inhibitors designed essentially to prevent the loss of cholinergic function. The multifactorial AD pathology calls for Multitarget-directed ligands (MTDLs) to follow up on various components of the disease. Considering this approach, other related AD targets were also selected. Structure-based virtual screening was relied upon for the identification of lead compounds with anti-AD effect. METHOD: Several chemoinformatics approaches were used in this study, reporting four multi-target inhibitors: MCULE-7149246649-0-1, MCULE-6730554226-0-4, MCULE-1176268617-0-6 and MCULE-8592892575-0-1 with high binding energies that indicate better AChE inhibitory activity. Additional in-silico analysis hypothesized the abundant presence of aromatic interactions to be pivotal for interaction of selected compounds to the acetyl-cholinesterase. Additionally, we presented an alternative approach to determine protein-ligand stability by calculating the Gibbs-free energy change over time. Furthermore, this allows to rank potential hits for further in-vitro testing. RESULTS AND CONCLUSION: With no predicted indication of adverse effects on humans, this study unravels four active multi-target inhibitors against AChE with promising affinities and good ADMET profile for the potential use in AD treatment.

Illness Perceptions in Patients of Schizophrenia: A Preliminary Investigation from Lahore, Pakistan.

BACKGROUND AND OBJECTIVE: Patient's perception of their illness influences their healthcare decisions. The objectives of this study were to explore patient's own beliefs about their illness (Schizophrenia) and perceived social support, and its impact on their attitudes toward pharmacological treatment in Lahore, Pakistan. METHODS: This study was conducted at Mayo Hospital Lahore from March to September 2016. Hundred individuals suffering from Schizophrenia completed four questionnaires; a socio-demographic questionnaire, the Illness Perception Questionnaire for Schizophrenia(IPQ-S), Drug attitude Inventory-10 (DAI) and Multidimensional Scale of Perceived Social Support (PSS). RESULTS: Stress, family problems, lack of friends & financial worries were endorsed strongly by patients as cause of their mental illness. Ambiguity regarding their mental illness duration and personal control was observed. Patients' perceived significant negative consequences, negative emotional response, as well as had poor understanding of their mental illness and treatment effectiveness. Statistically significant gender differences in treatment control and illness coherence subscales of IPQS were observed. Drug attitude inventory was positively correlated with Treatment control subscale (p < .01) and negatively correlated with Illness coherence subscale of IPQS (p < .05). The negative consequences subscale and perceived social support was negatively correlated (p < .01). CONCLUSION: Patient's perception about their own illness is predictor of their drug taking attitude and perceived social support. Study results should help to develop new interventions to correct inaccurate beliefs in patients with schizophrenia to improve illness outcome.