Fragment-Based Drug Design to Discover Novel Inhibitor of Dipeptidyl Peptidase-4 (DPP-4) as a Potential Drug for Type 2 Diabetes Therapy

Eka Gunarti Ningsih, Muhammad Fauzi Hidayat, Usman Sumo Friend Tambunan

Research output: Chapter in Book/Report/Conference proceedingConference contributionpeer-review

Abstract

Diabetes mellitus is among the highest cause of death in the world. Medicinal treatment of diabetes mellitus can be achieved by inhibiting Dipeptidyl Peptidase-4 (DPP-4). This enzyme rapidly inactivates incretin, which acts as a glucoregulatory hormone in the human body. Fragment-based drug design through computational studies was conducted to discover novel DPP-4 inhibitors. About 7,470 fragments out of 343,798 natural product compounds were acquired from applying Astex Rule of Three. The molecular docking simulation was performed on the filtered fragments against the binding site of DPP-4. Fragment-based drug design was carried out by growing new structures from the potential fragments by employing DataWarrior software. The generated ligand libraries were evaluated based on the toxicity properties before underwent virtual screening, rigid, and induced-fit molecular docking simulation. Selected ligands were subjected to the pharmacological and toxicological property analysis by applying DataWarrior, Toxtree, and SWISSADME software. According to the ligand affinity, which based on the ∆G binding value and molecular interaction along with the pharmacological properties of the ligand, two best ligands, namely FGR-2 and FGR-3, were chosen as the novel inhibitor of DPP-4. Further in vitro, in vivo, and clinical trial analysis must be executed in order to validate the selected ligands therapeutic activity as drug candidates for type 2 diabetes.

Original languageEnglish
Title of host publicationBioinformatics and Biomedical Engineering - 7th International Work-Conference, IWBBIO 2019, Proceedings
EditorsFrancisco Ortuño, Olga Valenzuela, Ignacio Rojas, Fernando Rojas, Francisco Ortuño
PublisherSpringer Verlag
Pages14-24
Number of pages11
ISBN (Print)9783030179373
DOIs
Publication statusPublished - 1 Jan 2019
Event7th International Work-Conference on Bioinformatics and Biomedical Engineering, IWBBIO 2019 - Granada, Spain
Duration: 8 May 201910 May 2019

Publication series

NameLecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics)
Volume11465 LNBI
ISSN (Print)0302-9743
ISSN (Electronic)1611-3349

Conference

Conference7th International Work-Conference on Bioinformatics and Biomedical Engineering, IWBBIO 2019
Country/TerritorySpain
CityGranada
Period8/05/1910/05/19

Keywords

  • Dipeptidyl Peptidase-4
  • Fragment-based drug design
  • In silico
  • Natural compounds
  • Type 2 diabetes

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