Multitargeted Molecular Docking and Dynamic Simulation Studies of Bioactive Compounds from Rosmarinus officinalis against Alzheimer’s Disease

Alzheimer’s disease (AD) has been associated with the hallmark features of cholinergic dysfunction, amyloid beta (Aβ) aggregation and impaired synaptic transmission, which makes the associated proteins, such as β-site amyloid precursor protein cleaving enzyme 1 (BACE I), acetylcholine esterase (AChE) and synapsin I, II and III, major targets for therapeutic intervention. The present study investigated the therapeutic potential of three major phytochemicals of Rosmarinus officinalis, ursolic acid (UA), rosmarinic acid (RA) and carnosic acid (CA), based on their binding affinity with AD-associated proteins. Detailed docking studies were conducted using AutoDock vina followed by molecular dynamic (MD) simulations using Amber 20. The docking analysis of the selected molecules showed the binding energies of their interaction with the target proteins, while MD simulations comprising root mean square deviation (RMSD), root mean square fluctuation (RMSF) and molecular mechanics/generalized born surface area (MM/GBSA) binding free energy calculations were carried out to check the stability of bound complexes. The drug likeness and the pharmacokinetic properties of the selected molecules were also checked through the Lipinski filter and ADMETSAR analysis. All these bioactive compounds demonstrated strong binding affinity with AChE, BACE1 and synapsin I, II and III. The results showed UA and RA to be potential inhibitors of AChE and BACE1, exhibiting binding energies comparable to those of donepezil, used as a positive control. The drug likeness and pharmacokinetic properties of these compounds also demonstrated drug-like characteristics, indicating the need for further in vitro and in vivo investigations to ascertain their therapeutic potential for AD.     

Official proficiency tests of the organisation for the prohibition of chemical weapons: current status and future directions

The Organisation for the Prohibition of Chemical Weapons (OPCW) has been organising and conducting Official Proficiency Tests (PT) since 1996 in accordance with ILAC-G13 to certify laboratories for the analysis of authentic samples under the provision of Chemical Weapons Convention. The tests are part of a mechanism to ensure that there are laboratories that have proven competence in the analysis of chemicals related to the Convention. Laboratories that have successfully completed the tests are designated by the Director General of the OPCW for analysis of authentic samples. To maintain the Designated Laboratory status, a laboratory must take and pass at least one of the two proficiency tests offered per calendar year. Unlike many proficiency tests, the OPCW PT is qualitative, that is the laboratories must determine if any of a very large set (essentially infinite) of chemicals relevant to the Convention are present in the samples. The tests are organised with the assistance of two laboratories, one preparing the test samples, and the other evaluating the test results. The paper provides an overview of the current status of these PTs and outlines salient features regarding procedure and scope of tests, selection of assisting laboratories, scoring and performance rating of participating labs. The emerging issues are also briefly discussed.