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

Introduction: Aminopeptidase N (APN) is one of the most critical metalloenzymes in the body belongingto the M family, containing zinc atoms (Zn۲ +). This enzyme attaches to the n-terminus of amino acids anddestroys amino acids and proteins. APN plays a vital role in angiogenesis, and tumor metastasis. Theexpression level of this enzyme is increased in most cancers of the stomach, pancreas, prostate, and kidneyand 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, itsinhibitory synthesis has become attractive [۲, ۳]. Tetralones such as benzosuberon derivatives, as a potentAPN non-peptide inhibitor, competitively and selectively inhibit the enzyme aminopeptidase N. Theapplication of bioinformatics could help to rational drug design and identification of new potent leadcompounds. In this project, APN inhibitory activity of ۳۰ Benzosuberon derivatives was investigated bymolecular docking studies, and the best compounds were selected to evaluate the enzymatic assay.Methods: The Crystal structure of APN, with the PDB ID of ۴FKK and resolution of ۲.۶۰ Aº was achievedfrom Protein Data Bank (www.rcsb.org). After validation, all derivatives were investigated by dockingstudies. Finally, compounds with best docking score have been selected for synthesis and evaluation byenzymatic assay.Results and Discussion: Here molecular docking studies were used to identify new compounds withinhibitory effects on APN. The binding energy and main interactions between the benzosuberon derivativesand APN binding pocket were precisely investigated in detail. Compounds with appropriate docking scoreselected for enzymatic assay. Selected compounds can be considered as a proper candidate in order to developnew APN inhibitors.

کلیدواژه ها:

Inhibitor ، Molecular Docking ، Aminopeptidase N ، Benzosuberone ، Cancer