Identification of anti-Parkinson's Disease Lead Compounds from Aspergillus ochraceus Targeting Adenosin Receptors A2A.

ChemistryOpen
Linzhen HuYonghui Zhang

Abstract

Two novel alkaloids compounds together with fifteen know metabolites were identified from Aspergillus ochraceus. The stereochemistry features of the new molecules were determined via HRESIMS, NMR, ECD, and XRD analyses. Amongst these, compounds two compounds exhibited potential efficacy as anti-Parkinson's disease with the EC50 values of 2.30 and 2.45 μM, respectively. ADMET prediction showed that these compounds owned favorable drug-like characteristics and safe toxicity scores towards CNS drugs. Virtual screening analyses manifested that the compounds exhibited not only robust and reliable interactions to adenosine receptors A2A , but also higher binding selectivity to A2A receptors than to A1 and A3 receptors. Molecular dynamics simulation demonstrated the reliability of molecular docking results and the stability of the complexes obtained with the novel compounds and A2A receptors in natural environments. It is the first time that anti-PD lead compounds have been identified from Aspergillus ochraceus and targeting adenosine A2A receptors.

References

Jul 1, 1992·Journal of Natural Products·F S de GuzmanP F Dowd
Jul 8, 1999·Journal of Natural Products·L Rahbaek, J Breinholt
Dec 11, 1999·Nucleic Acids Research·H M BermanP E Bourne
Feb 15, 2001·Journal of Natural Products·J DaiM S Butler
Oct 25, 2001·The Journal of Organic Chemistry·Lisa RahbaekCarsten Christophersen
Mar 25, 2005·Journal of Natural Products·Tayyab A MansoorJee H Jung
Apr 10, 2008·British Medical Bulletin·C A Davie
Dec 5, 2008·Journal of Natural Products·Sachiko TsukamotoTomihisa Ohta
Jan 1, 2009·Nature Chemistry·Kenneth A MillerRobert M Williams
Jun 22, 2010·Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology·Hongrong XieLinsen Hu
May 15, 2012·Drug Discovery Today·Alan M Palmer, Mohammad S Alavijeh
Mar 1, 1986·Mycotoxin Research·I Delgadillo
May 25, 2013·Journal of Natural Products·Jiang PengShu-Hua Qi
Oct 30, 2013·Journal of Medicinal Chemistry·Manuel de Lera RuizJunying Zheng
Jun 5, 2014·Natural Product Research·Xiang-Hong LiuNai-Yun Ji
Dec 1, 2004·Drug Discovery Today. Technologies·Christopher A Lipinski
Aug 5, 2017·Natural Product Research·Zong-Bo TongZhan-Jun Ren
Feb 21, 2018·Endocrine Connections·Chanyang Kim, Seungjoon Park
Feb 27, 2018·Chemistry & Biodiversity·Huiling WenYonghui Zhang
Jun 10, 2018·The Journal of Antibiotics·Shamil Sh AfiyatullovAnton N Yurchenko
Apr 13, 2019·Saudi Pharmaceutical Journal : SPJ : the Official Publication of the Saudi Pharmaceutical Society·Mohammad K ParvezMohammed F Alajmi

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Software Mentioned

PyMOL
LibDockScore
PyMOL Molecular Graphics System
MGLTools
AutoDock
CDOCKER
Graphpad Prism
Gaussian
LibDock
3EML

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