Ligand-Based and Docking-Based Virtual Screening of MDM2 Inhibitors as Potent Anticancer Agents-Reference-Cited by-同舟云学术

Ligand-Based and Docking-Based Virtual Screening of MDM2 Inhibitors as Potent Anticancer Agents

Published:2021-08-05 Issue: Volume:2021 Page:1-9
ISSN:1748-6718
Container-title:Computational and Mathematical Methods in Medicine
language:en
Short-container-title:Computational and Mathematical Methods in Medicine

Author:

Li Bing-Hui¹,Ge Jun-Qi²,Wang Ya-Li¹^ORCID,Wang Li-Jun¹,Zhang Qi¹,Bian Cong³

Affiliation:

1. School of Pharmacy and Life Sciences, Jiujiang University, Jiujiang 332000, China

2. School of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China

3. Institute of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050, China

Abstract

A ligand-based and docking-based virtual screening was carried out to identify novel MDM2 inhibitors. A pharmacophore model with four features was used for virtual screening, followed by molecular docking. Seventeen compounds were selected for an in vitro MDM2 inhibition assay, and compounds AO-476/43250177, AG-690/37072075, AK-968/15254441, AO-022/43452814, and AF-399/25108021 showed promising MDM2 inhibition activities with

K_{i}

values of 9.5, 8.5, 23.4, 3.2, and 23.1 μM, respectively. Four compounds also showed antiproliferative activity, and compound AO-022/43452814 was the most potent hit with IC50 values of 19.35, 26.73, 12.63, and 24.14 μM against MCF7 (p53 +/+), MCF7 (p53 -/-), HCT116 (p53 +/+), and HCT116 (p53 -/-) cell lines, respectively. Compound AO-022/43452814 could be used as a scaffold for the development of anticancer agents targeting MDM2.

Funder

Natural Science Foundation of Jiangxi Province

Publisher

Hindawi Limited

Subject

Applied Mathematics,General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,Modelling and Simulation,General Medicine

Link

http://downloads.hindawi.com/journals/cmmm/2021/3195957.pdf

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