Design Synthesis and Biological Evaluation of Heterocycles Targeting Dipeptidyl Peptidase 4 DPP 4 for Management of Type 2 Diabetes

Abstract

newlineThe research work titled Design, Synthesis and Biological Evaluation of Heterocycles Targeting Dipeptidyl Peptidase-4 (DPP-4) for management of Type 2 Diabetes is divided into 7 chapters mentioned in brief as follows. newlineChapter 1 outlines historical aspects of diabetes, epidemiology, prevalence, classification and current therapies for management of Type 2 Diabetes (T2D). Novel therapies under development for management of T2D encompassing targets and related New Chemical Entities (NCEs) are described. newlineChapter 2 begins with role of incretin hormones in blood sugar control, effect of Dipetidyl Peptidase-4 (DPP-4) and impact of DPP-4 inhibition on blood sugar levels. It is followed by classification systems of DPP-4 inhibitors, Gliptins and discussion about peptidomimetic and non-peptidomimetic inhibitors with importance on diversity in their structure. Chapter is concluded with advantages and limitations of Gliptins. newlineAim of present work was envisaged to exploit computer-aided drug design approaches to identify new small molecules as DPP-4 inhibitors. Aim and objectives of the research work are briefed in chapter 3. newlineChapter 4 is detailed on various computational tools to identify new molecules that can inhibit DPP-4. In present work, various X-ray crystal structures of DPP-4 enzymes were analyzed to study their active site and interaction pattern. Following the virtual screening, methodologies were used for identification of new synthetic small molecules having the affinity for DPP-4 inhibitors. newlineCommon feature pharmacophore approach was used in combination with docking to screen the commercial compound library for searching new templates that may inhibit DPP-4, and few selected hits were subjected to in-vitro DPP-4 enzyme inhibition assay. Docking poses obtained for few hit compounds were confirmed by molecular dynamics simulation. In second computational approach molecular dynamics structure-based pharmacophore approach was used to generate receptor-based pharmacophore using multiple DPP-4 protein newlineiii newline