Three-Dimensional Quantitative Structure-activity Relationship Research Of Anti-type 2 Diabetes Mellitus Compounds

Nowadays,it is critical that type 2 diabetes mellitus(T2DM)has become a major problem which is affecting human health.According to recent research there are more than 270 million patients who have T2 DM around the world.The number of patients with T2 DM is expected to be 400 million till 2030.Finding a way to deal with T2 DM is hanging over researcher’s head.Recently,computer-aided drug design(CADD)is becoming more and more mature.Three-dimensional quantitative structure-activity relationship(3D-QSAR)model of drug-like compounds could be the basis for drug design and lead-compound transformation.The 3D-QSAR of anti-T2 DM have become more and more important position because of the numerous targets to T2 DM.In this paper we use CADD to construct 3D-QSAR model to 3 different target of T2 DM.Compare molecular force field,docking,rational molecular design are used to build the models.In the review,I summarize the popular anti-T2 DM targets,review the biological activity experiments,crystal complex structure analysis and CADD methods researchers have made.In the first part,3D-QSAR model is built using comparative molecular force field(Co MFA)for sodium glucose co-transporter 2(SGLT2)inhibitor which did not have crystal complex structure.The cross-validation coefficient reached 0.318,the model is reliable.The model shows that force filed have a critical effect to activity.The model could be used to provide new SGLT2 inhibitor.In the second part,based on Co MFA model of 11β-hydroxy steroid dehydrogenase(11β-HSD)inhibitor docking of ligand and receptor is used to find the 3D-QSAR.It is CDOCKER that could show the interaction of inhibitor and 11β-HSD.A:172ALA,A:216GLY play a critical role in the molecular interaction and hydrogen bond formation.A:180VAL A:183TYR may help electrostatic interaction with the inhibitor.The interaction model help to make comment to structural transformation of 11β-HSD inhibitors.Last but not the least,pharmacokinetic design of glucosidase(GK)agonist was carried out by the former two parts,The GK agonists are modified using growscaffold pilot of CADD based on chemical synthesis theory.The activity of agonists are predicted with the 3D-QSAR model made by Co MFA,some of which is expected to have higher biological activity than the lead-compound,it is expected to be new anti-T2 DM drug.