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

[ Vol. 18 , Issue. 2 ]

Author(s):

Parasuraman Pavadai*, Suresh Ramalingam, Theivendren Panneerselvam, Selvaraj Kunjiappan, Pandurangan Perumal, Vasudevan Mani, Govindaraj Saravanan, Veerachamy Alagarsamy, Damodar Nayak Ammunje and Jithendra Chimakurthy   Pages 160 - 168 ( 9 )

Abstract:


Background: 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, DPPS, enzyme inhibition, AChE, BACE1.

Affiliation:

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, M.S. Ramaiah University of Applied Sciences, MSR Nagar, Bengaluru-560054, Karnataka, Department of Pharmacy, Annamalai University Faculty of Engineering and Technology, Annamalai Nagar, Chidambaram, Tamil Nadu-608002, Department of Research and Development, Saraswathi Institute of Medical Sciences, NH-24, Anwarpur, Pilkhuwa, Hapur-245304, Uttar Pradesh, Sir CV Raman-KS Krishnan International Research Center, Kalasalingam University, Krishnankoil-626126, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Asian Institute of Medicine, Science and Technology (AIMST) University, 08100 Bedong, Kedah DarulAman, Department of Pharmacology and Toxicology, College of Pharmacy, Qassim University, Buraidah, 51452, Department of Pharmaceutical Chemistry, MNR College of Pharmacy, Fasalwadi, Sangareddy- 502294, Telangana, Department of Pharmaceutical Chemistry, MNR College of Pharmacy, Fasalwadi, Sangareddy- 502294, Telangana, Department of Pharmacology, Faculty of Pharmacy, M.S. Ramaiah University of Applied Sciences, MSR Nagar, Bengaluru-560054, Karnataka, Department of Pharmaceutical Sciences, Vignan’s Foundation for Science, Technology & Research, Guntur-522213, Andhra Pradesh

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