Screening natural product database for identification of potential inhibitors of beta Secretase; a key enzyme of Alzheimer’s disease

Abstract

Alzheimer¡¦s disease is a most common amyloid-associated disorder, irreversible, progressive brain disorders that leads to change in nerve cells destroying the thinking, memory, remembering, reasoning and skills of individuals. The symptom of Alzheimer¡¦s, disease generally appears in the individuals having age more than 65 years. The neuropathological hallmarks of AD include presence of senile plaques (NP) and neurofibrillary tangles (NFT). Amyloid Beta precursor protein cleaving enzyme (BACE-1) or Memapsin-2 is a single-membrane protein belongs to the Aspartyl protease family, responsible for the processing of the amyloid Precursor protein (APP). The cleavage of APP by BACE-1 leads to production of two peptide fragments Amyloid beta peptide (AƒÒ) 40 and 42. AƒÒ42 is thought to be responsible for the neurotoxicity and amyloid plaque formation in Alzheimer¡¦s disease (AD). Thus BACE-1 will be an important drug target for the generation of inhibitors that lower A£]. We aim to identify potential natural product inhibitors of beta secretase which can be further developed as drug to treat Alzheimer¡¦s disease. Here, we have performed in silico virtual screening approach of a natural product database consists of 800 different chemical molecules. Beta secretase (PDB ID: 1FKN) was used in screening process, and docking studies to identify potential lead compounds. The sorting of compound were done based upon their binding energy and top 50 ranked protein- inhibitor complexes were selected. We have reported some compound like Spermine, Netilmicinsulfate, and Spermidine Trihydrochloride molecule which could be potential inhibitors of beta secretase. The ligplot image also provided some idea about the inhibitors that they can attain at the active site of beta secretase.