Citation: Hong-Mei GUO, Le FU, Guang-Ping LI, Mao SHU, Zhi-Hua LIN. Discovery of Novel Acetaldehyde Dehydrogenase 1A1 (ALDH1A1) Inhibitors by Utilizing 3D-QSAR, Molecular Docking and Molecular Dynamics Simulation[J]. Chinese Journal of Structural Chemistry, ;2021, 40(5): 549-564. doi: 10.14102/j.cnki.0254–5861.2011–2982 shu

Discovery of Novel Acetaldehyde Dehydrogenase 1A1 (ALDH1A1) Inhibitors by Utilizing 3D-QSAR, Molecular Docking and Molecular Dynamics Simulation

School of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing 400054, China

Corresponding author: Mao SHU, maoshu@cqut.edu.cn Zhi-Hua LIN, zhlin@cqit.edu.cn
Received Date: 15 September 2020
Accepted Date: 5 October 2020

Fund Project: the key project of Chongqing natural science foundation cstc2015jcyjBX0080

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Acetaldehyde dehydrogenase 1A1 is a hopeful therapeutic target to ovarian cancer. In this present work, 3D-QSAR, molecular docking and molecular dynamics (MD) simulations were implemented on a series of quinoline-based ALDH1A1 inhibitors to investigate novel acetaldehyde dehydrogenase 1A1 inhibitors as anti-cancer adjuvant drugs for ovarian cancer. Two reliable CoMFA (Q² = 0.583, R² = 0.967) and CoMSIA (Q² = 0.640, R² = 0.977) models of ALDH1A1 inhibitors were established. Novel ALDH1A1 inhibitors were predicted by the 3D-QSAR models. Molecular docking reveals important residues for protein-compound interactions, and the results revealed ALDH1A1 inhibitors had stronger electrostatic interaction and binding affinity with key residues of protein, such as Phe171, Val174 and Cys303. Molecular dynamics simulations further verified the results of molecular docking. The above information provided significant guidance for the design of novel ALDH1A1 inhibitors.
- 3D-QSAR,
- molecular docking,
- molecular dynamics simulation,
- ALDH1A1 inhibitors
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