Research Paper Volume 12, Issue 12 pp 11349—11363
Computational study on new natural compound inhibitors of indoleamine 2,3-dioxygenase 1
- 1 Department of Neurosurgery, The First Hospital of Jilin University, Changchun, China
- 2 Institute of Zoology, Chinese Academy of Sciences, Chaoyang, China
- 3 College of Basic Medical Sciences, Jilin University, Changchun, China
- 4 Clinical College, Jilin University, Changchun, China
- 5 Department of Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA
- 6 Department of Orthopaedic Surgery, Xijing Hospital, The Fourth Military Medical University, Xi’an, China
- 7 Department of Orthopaedic Surgery, The First Hospital of Jilin University, Changchun, China
- 8 Department of Neurology, The First Hospital of Jilin University, Changchun, China
Received: July 31, 2019 Accepted: April 7, 2020 Published: June 22, 2020
https://doi.org/10.18632/aging.103113How to Cite
Copyright © 2020 Jiang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Indoleamine 2,3-Dioxygenase (IDO), is a speed limiting enzyme that catalyzes the decomposition and metabolism of Tryptophan along Tryptophan-IDO-Kynurenine pathway [1]. Tryptophan is a necessary amino acid for activating cell growth and metabolism. Additionally, the insufficiency of Tryptophan can lead to immune system dysfunction. Raising the level of Indoleamine 2,3-Dioxygenase protein can promote stagnation and apoptosis of effector T cells [2].
In contrast, the decline in the number of effect T cells naturally protects cancer cells from attack. Therefore, Indoleamine 2,3-Dioxygenase is a potential target for tumour immunotherapy, such as melanoma, ovarian cancer, lung cancer, leukaemia, and so on, especially in solid tumours [3]. In the study, we have done sets of virtual screening aided by computer techniques in order to find potentially effective inhibitors of Indoleamine 2,3-Dioxygenase. Firstly, screening based on structure was carried out by Libdock. Then, ADME (adsorption, distribution, metabolism, excretion) and toxicity prediction were also analyzed. Molecular docking and 3D-QSAR pharmacophore generation were used to study the mechanism of these compounds and Indoleamine 2,3-Dioxygenase’s binding. A molecular dynamic analysis was carried out to assess if these potential compound’s binding is stable enough. According to the results of the analysis above, two potential compounds (ZINC000012495022 and ZINC000003791817) from the ZINC database were discovered to interact with Indoleamine 2,3-Dioxygenase with appropriate energy and proved to be none toxic. The study offered valuable information of Indoleamine 2,3-Dioxygenase inhibitor-based drug discovery in cancer therapy by increasing the activity of T cells and releasing immunity suppression [4, 5].