Synthesis of piperidine-4-one Derivative Containing Dipeptides: An Acetyl cholinesterase and β-secretase Inhibitor

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Author(s): Parasuraman Pavadai*, Suresh Ramalingam, Theivendren Panneerselvam, Selvaraj Kunjiappan, Pandurangan Perumal, Vasudevan Mani, Govindaraj Saravanan, Veerachamy Alagarsamy, Damodar Nayak Ammunje.

Journal Name: Anti-Infective Agents

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Introduction: With the goal of developing Alzheimer's disease therapeutics, we have designed and synthesized novel piperidone fused dipeptide (DPPS) derivatives possessing dual action such as acetylcholinesterase (AChE) and beta-amyloid peptide (Aβ) aggregation inhibition. Designed peptide was synthesized by solid phase peptide synthesis using FMOC chemistry protocol and characterized by mass spectroscopy.

Methods: The amino acid sequence in peptide was analyzed by LC-MS-MS. In silico docking analysis was carried out using GLIDE software. The docking score using GLIDE was found to be -7.88 against AChE and -9.74 against BACE1 enzyme. In vitro enzyme inhibition assay was carried out for AChE enzyme and BACE1 enzyme.

Results: The IC50 values of AChE inhibition and BACE1 of DPPS were found to be 0.4796 μM/ml and 0.0154 μM/ml, respectively. The correlation of in silico and in vitro results showed that DPPS possessed a greater ability to inhibit BACE1 enzyme.

Keywords: Alzheimers disease, Peptides, In silico modeling, Enzyme inhibition, AChE, BACE1

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(E-pub Ahead of Print)
DOI: 10.2174/2211352517666190405155505