Discovery of Novel Alpha-Amylase Inhibitors for Type II Diabetes Mellitus Through the Fragment-Based Drug Design

Yulianti, Agustinus Corona Boraelis Kantale, Usman Sumo Friend Tambunan

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

Abstract

Diabetes mellitus is a metabolic disorder leading to hyperglycemia and organ damage. In 2017, the International Diabetes Federation (IDF) reported that about 425 million people living with diabetes, most of which suffer from type 2 diabetes mellitus. The drug development for controlling glucose level is crucial to treat people with type 2 diabetes mellitus. Alpha-amylase plays an imperative role in carbohydrate hydrolysis. Hence, the inhibition of alpha-amylase, which halt the glucose absorption, can be a promising pathway for developing type 2 diabetes mellitus drugs. Natural product has been known as the lead drugs for various diseases. In this research, the fragment merging drug design was performed by employing both the existing drug, voglibose, as the template and the natural product compounds to generate newly constructed ligands. The fragments were acquired from ZINC15 natural product database and then were screened according to Astex’s Rules of Three, pharmacophore properties, and molecular docking simulation. The 482 selected fragments were evaluated under Lipinski’s Rule of Five and toxicity effects using DataWarrior software. The ligands underwent molecular flexible docking simulation followed by the ADME-Tox prediction by using Toxtree, AdmetSAR, and SwissADME software. In the end, two lead compounds showed the best properties as an alpha-amylase inhibitor based on their low ΔG binding , acceptable RMSD score, favorable pharmacological properties, and molecular interaction.

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
Pages25-35
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
CountrySpain
CityGranada
Period8/05/1910/05/19

Keywords

  • Alpha-amylase
  • Fragment-based drug design
  • Type 2 diabetes mellitus

Fingerprint Dive into the research topics of 'Discovery of Novel Alpha-Amylase Inhibitors for Type II Diabetes Mellitus Through the Fragment-Based Drug Design'. Together they form a unique fingerprint.

Cite this