title: Using computer-aided drug design and medicinal chemistry strategies in the fight against diabetes.
abstract: The aim of this work is to present a simple, practical and efficient protocol for drug design, in particular Diabetes, which includes selection of the illness, good choice of a target as well as a bioactive ligand and then usage of various computer aided drug design and medicinal chemistry tools to design novel potential drug candidates in different diseases. We have selected the validated target dipeptidyl peptidase IV (DPP-IV), whose inhibition contributes to reduce glucose levels in type 2 diabetes patients. The most active inhibitor with complex X-ray structure reported was initially extracted from the BindingDB database. By using molecular modification strategies widely used in medicinal chemistry, besides current state-of-the-art tools in drug design (including flexible docking, virtual screening, molecular interaction fields, molecular dynamics, ADME and toxicity predictions), we have proposed 4 novel potential DPP-IV inhibitors with drug properties for Diabetes control, which have been supported and validated by all the computational tools used herewith.
authors.affiliation: Departamento de Ciencias Farmaceuticas, Faculdade de Ciencias Farmaceuticas de Ribeirao Preto, Universidade de Sao Paulo, Av. do Cafe, s/n, Monte Alegre, 14040-903, Ribeirao Preto-SP, Brazil.
authors.forename: Evandro P
authors.initials: EP
authors.lastname: Semighini
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Resende
authors.forename: Peterson
authors.initials: P
authors.lastname: de Andrade
authors.forename: Pedro A B
authors.initials: PA
authors.lastname: Morais
authors.forename: Ivone
authors.initials: I
authors.lastname: Carvalho
authors.forename: Carlton A
authors.initials: CA
authors.lastname: Taft
authors.forename: Carlos H T P
authors.initials: CH
authors.lastname: Silva
mesh_terms: D001665:Binding Sites; D002626:Chemistry, Pharmaceutical; D017076:Computer-Aided Design; D016208:Databases, Factual; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000737:chemistry; D015195:Drug Design; D006801:Humans; D007004:Hypoglycemic Agents / Q000737:chemistry* / Q000627:therapeutic use; D008024:Ligands; D008968:Molecular Conformation; D056004:Molecular Dynamics Simulation
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D008024:Ligands; D018819:Dipeptidyl Peptidase 4