In-Silico Docking, Design and Synthesis of Certain Benzotriazole Derivatives and Study of their Antialzheimer’s Activity

The present Study was focused on predicting the protein-ligand interactions, design, synthesis and evaluation of substituted Benzotriazole derivatives as possible anticholinesterase inhibitors. IN SILICO STUDIES: • Selection of target: Cholinesterase inhibitors was selected as the target for Anti-Alzheimer’s activity. The corresponding target was downloaded from RCSB protein databank (PDB: 4EY7, & 4BDS). • Selection of lead: The lead Benzotriazole was selected based on several literature reviews. Derivatives of Benzotriazole, Benzotriazole hybrids were reported to have anticholinesterase activity. • Lead optimization: Lead optimization was done by observing in-silico ADMET studies and computation of molecular and ADME properties. All the selected ligands had good ADMET properties and hence were eligible for the further study. • Docking: Molecular docking studies were performed using glide software. The ligands were docked with the target (4EY7 & 4BDS). The ligands BA-1A to 1D and BE-2A to 2D was showing best docked pose. SYNTHESIS: In this present work two schemes were developed for the compounds to be synthesized. Eight new compounds were synthesized. Benzotriazole was the starting compounds for both the schemes. In the first scheme, O-phenylenediamine was reacted with sodium nitrite and acetic acid to form Benzotriazole. By treating substituted benzoic acid with thionyl chloride to form a substituted acid chloride and further Benzotriazole and substituted acid chloride reacts to obtain desired products. In second scheme, synthesized Benzotriazole was treated with Ethyl chloroacetate to form intermediate ethyl-1H-Benzotriazoyl-acetate and further treated with various primary amines to obtain desired products. PHYSICAL CHARACTERIZATION: Melting point of newly synthesized compounds were determined. Rf values were determined by fixing various suitable solvent system on precoated silica gel G plates. The structure was finally characterized by UV, IR, Mass, and 1HNMR Spectra. IN-VITRO ENZYME INHIBITORY ACTIVITY: Neurodegenerative disease is characterized by decrease in the level of neurotransmitters, oxidative stress and neuro inflammation in brain, mostly the treatments are based on enhancing the Cholinergic function in brain there by improve the level of neuro transmitter from break down. Cholinesterase inhibitors were developed based on cholinergic hypothesis of Alzheimer’s disease, where Cholinesterase inhibitors reduce the degradation of the synaptic acetylcholine; improve level of acetylcholine in a dose-dependent manner. AChE and BuChE are two different enzymes located in brain that responsible for hydrolysis. Rivastigmine; dual AChE and BuChE inhibitors where it was used as standard. All the newly synthesized compounds were screened for anticholinesterase activity using Ellman’s method and all the compounds showed moderate activity. It was observed that the nature and size of the substituents play a role in influencing the activity of the compounds. The compounds BA-D and BE-2A showed good percentage inhibition for AChE activity when compared to the standard Rivastigmine. Similarly, the compounds BA-2C and BE-2A shows good percentage inhibition for BuChE activity when compared with the standard Rivastigmine. This clearly demonstrate that our compounds have potential to increase the level of acetyl choline and it could also be used in prevention and control of Alzheimer’s disease. CONCLUSION: After analyzing the results of the present work, following conclusions were made, The present work basically aims to identify the correct conformations of ligands in the active site protein and to predict the affinity of the ligand towards the protein. Structural based drug design approach proved to be a tool in minimizing the tedious drug discovery process. The In silico molecular and ADME properties was established the compounds to be pharmacokinetically active. QIKPROP was used for filtering the compounds and selecting the lead compounds. Docking results confirmed the possibility of Benzotriazole moiety to possess anticholinesterase activity. The binding energy obtained from docking study further confirmed the possibility of the affinity of the selected leads towards the enzyme Cholinesterase. The compounds were synthesized based on the developed scheme and good yields obtained. Synthesized compounds structures were confirmed by Melting point, Rf value, UV, IR, Mass and NMR spectra. All compounds were screened for anti-Alzheimer’s activity all the showed the better activity. Derivatives of Benzotriazole were proven as a potent anti-Alzheimer’s agents via anticholinesterase inhibition. Novel structure based drug design process helped to screen several compounds for specific activity. Present work could be considered as preliminary study of the titled moiety towards AChE & BuChE activity and further confirmation can be done by several site specific inhibitory actions

Detection of unattended and stolen objects in videos

Abstract-This research work presents an efficient approach of detecting unattended or stolen objects in live videos based on background subtraction and foreground analysis. The most common algorithm for performing background subtraction is the Gaussian Mixture model (GMM). An improved Multi-Gaussian Adaptive background model is employed for background subtraction to determine the static region. A simple split and merge method is used to detect the static region from which the static objects are identified. The time and presence of static objects, which may be either unattended or stolen, are informed by sending a mail and SMS to the security officials. Also, Haralick's texture operators are employed for images to identify objects under low contrast situations. The system is efficient to run in real time and produce good results