ABSTRACT

Globally there are over 48 million people who grieve from Alzheimer’s disease (AD), symptomatic treatment exists but there is no cure for it. Due to that, we wish to design suitable Tacrine analogs as anti-Alzheimer molecules for the AChE target using computational tools. AChE was carefully chosen as a target because inhibitors of AChE were effective and proven their efficacy in the management of dementia and mitigation of other symptoms. Extraction of lead molecules for Alzheimer’s target (AChE) can be done by ligand - ligand similarity through the PubChem database and performed docking based virtual screening by AutoDock Vina. Based on the binding energy, we prioritized several lead molecules and collected their experimental LD50 from the literature. Later QSAR model was built by applying correlation regression between experimental and predicted LD50 using the EasyQSAR tool. The six designed new analogs (T1-T6) is based on the molecular modification of Tacrine which contain’s a planner tricyclic ring system. Pharmacokinetic and toxicity studies were done for all the molecules to find drug likeliness by Mobyle@rpbs portal and Osiris property explorer. Molecular Docking was done with DockThor and AutoDock Vina separately. Acetylcholinesterase (1ACJ) was considered as target and six designed tacrine derivatives were considered as ligands. From the docking results, it was found that the designed tacrine-like analogs displays better binding affinity and less toxicity than standard tacrine. We, therefore, propose that the above six molecules may act as potent AChE inhibitors. Keywords: AutoDock Vina, EasyQSAR, PubChem, Molecular docking, Osiris Property Explorer, Virtual screening
Publication date: 01/10/2021

https://ijbpas.com/pdf/2021/October/MS_IJBPAS_2021_OCT_SPCL_1023.pdf

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https://doi.org/10.31032/IJBPAS/2021/10.10.1023