5 years ago

Molecular modeling and statistical analysis in the design of derivatives of human dipeptidyl peptidase IV

Gabriela B. dos Santos, Cleydson B.R. Santos, Carlos H.T.P. da Silva, Márcia S.F. Franco, Leonardo B. Federico, Alison L.E. Pereira

Human dipeptidyl peptidase IV (hDDP-IV) has a considerable importance in inactivation of glucagon-like peptide-1, which is related to type 2 diabetes. One approach for the treatment is the development of small hDDP-IV inhibitors. In order to design better inhibitors, we analyzed 5-(aminomethyl)-6-(2,4-dichlrophenyl)-2-(3,5-dimethoxyphenyl)pyrimidin-4-amine and a set of 24 molecules found in the BindingDB web database for model designing. The analysis of their molecular properties allowed the design of a multiple linear regression model for activity prediction. Their docking analysis allowed visualization of the interactions between the pharmacophore regions and hDDP-IV. After both analyses were performed, we proposed a set of nine molecules in order to predict their activity. Four of them displayed promising activity, and thus, had their docking performed, as well as, the pharmacokinetic and toxicological study. Two compounds from the proposed set showed suitable pharmacokinetic and toxicological characteristics, and therefore, they were considered promising for future synthesis and in vitro studies.

Publisher URL: http://www.tandfonline.com/doi/full/10.1080/07391102.2016.1277163

DOI: 10.1080/07391102.2016.1277163

You might also like
Discover & Discuss Important Research

Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.