1st International and 10th National Iranian Conference on Bioinformatics

Design, and molecular docking studies of novel benzosuberone derivatives as potential anticancer agents

Paper ID : 1384-ICB10

Authors:

Omid Ebrahimpour *

Department of Medicinal Chemistry, School of Pharmacy.Zanjan

Abstract:

Introduction
Aminopeptidase N (APN) is one of the most critical metalloenzymes in the body belonging to the M family, containing zinc atoms (Zn2 +). This enzyme attaches to the n-terminus of amino acids and destroys amino acids and proteins[1]. APN plays a vital role in angiogenesis, and tumor metastasis. The expression level of this enzyme is increased in most cancers of the stomach, pancreas, prostate, and kidney and causes cancer cells to multiply, so that APN can be a helpful marker in cancer diagnosis. As a result, inhibition of this enzyme can be very effective in inhibiting and controlling cancer. For this reason, its inhibitory synthesis has become attractive [2, 3]. Tetralones such as benzosuberon derivatives, as a potent APN non-peptide inhibitor, competitively and selectively inhibit the enzyme aminopeptidase N[4]. The application of bioinformatics could help to rational drug design and identification of new potent lead compounds. In this project, APN inhibitory activity of 30 Benzosuberon derivatives was investigated by molecular docking studies, and the best compounds were selected to evaluate the enzymatic assay.
Methods
The Crystal structure of APN, with the PDB ID of 4FKK and resolution of 2.60 Aº was achieved from Protein Data Bank (www.rcsb.org). After validation, all derivatives were investigated by docking studies. Finally, compounds with best docking score have been selected for synthesis and evaluation by enzymatic assay.
Results and Discussion
Here molecular docking studies were used to identify new compounds with inhibitory effects on APN. The binding energy and main interactions between the benzosuberon derivatives and APN binding pocket were precisely investigated in detail. Compounds with appropriate docking score selected for enzymatic assay. Selected compounds can be considered as a proper candidate in order to develop new APN inhibitors.

Keywords:

Inhibitor, Molecular Docking, Aminopeptidase N, Benzosuberone, Cancer

Status : Paper Accepted (Poster Presentation)