scholarly journals Potent and Selective Inhibitors of Human Monoamine Oxidase A from an Endogenous Lichen Fungus Diaporthe mahothocarpus

2021 ◽  
Vol 7 (10) ◽  
pp. 876
Author(s):  
Geum Seok Jeong ◽  
Prima F. Hillman ◽  
Myung-Gyun Kang ◽  
Sungbo Hwang ◽  
Jong-Eun Park ◽  
...  

Using 126 endogenous lichen fungus (ELF) extracts, inhibitory activities against monoamine oxidases (MAOs) and cholinesterases (ChEs) were evaluated. Among them, extract ELF29 of the endogenous fungus Diaporthe mahothocarpus of the lichen Cladonia symphycarpia showed the highest inhibitory activity against hMAO-A. Compounds alternariol (AT), 5′-hydroxy-alternariol (HAT), and mycoepoxydiene (MED), isolated from the extract, had potent inhibitory activities against hMAO-A with IC50 values of 0.020, 0.31, and 8.68 µM, respectively. AT, HAT, and MED are reversible competitive inhibitors of hMAO-A with Ki values of 0.0075, 0.116, and 3.76 µM, respectively. The molecular docking studies suggested that AT, HAT, and MED had higher binding affinities for hMAO-A (−9.1, −6.9, and −5.6 kcal/mol, respectively) than for hMAO-B (−6.3, −5.2, and −3.7 kcal/mol, respectively). The relative tight binding might result from a hydrogen bond interaction of the three compounds with a Tyr444 residue in hMAO-A, whereas no hydrogen bond interaction was proposed in hMAO-B. In silico pharmacokinetics, the three compounds showed high gastrointestinal absorption without violating Lipinski’s five rules, but only MED showed high probability to cross the blood–brain barrier. These results suggest that AT, HAT, and MED are candidates for treating neuropsychiatric disorders, such as depression and cardiovascular disease.

Chem ◽  
2021 ◽  
Author(s):  
Yue Xin ◽  
Sanmei Wang ◽  
Haibo Yuan ◽  
Tingting Hou ◽  
Wenkun Zhu ◽  
...  

2016 ◽  
Vol 18 (15) ◽  
pp. 10337-10345 ◽  
Author(s):  
Julien Diharce ◽  
Jérôme Golebiowski ◽  
Sébastien Fiorucci ◽  
Serge Antonczak

In the course of metabolite formation, some multienzymatic edifices, the so-called metabolon, are formed and lead through substrate channeling to a more efficient production of the natural compounds.


2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Sangeetha Srinivasan ◽  
D. V. L. Sarada

Antifungal activity of petroleum ether extract ofPsoralea corylifoliaL. seed, tested againstFusariumsp. namely,Fusarium oxysporum, Fusarium moniliforme,andFusarium graminearum, was evaluated by agar well diffusion assay. The chromatographic fractionation of the extract yielded a new phenyl derivative of pyranocoumarin (PDP). The structure of the PDP was confirmed using spectroscopic characterization (GC-MS, IR, and NMR), and a molecular mass ofm/z414 [M-2H]+with molecular formula C27H28O4was obtained. The PDP had a potent antifungal activity with a minimum inhibitory concentration of 1 mg/mL againstFusariumsp. Molecular docking using Grid-Based Ligand Docking with Energetics (GLIDE, Schrodinger) was carried out with the Tri101, trichothecene 3-O-acetyltransferase, as target protein to propose a mechanism for the antifungal activity. The ligand PDP showed bifurcated hydrogen bond interaction with active site residues at TYR 413 and a single hydrogen bond interaction at ARG 402 with a docking score −7.19 and glide energy of −45.78 kcal/mol. This indicated a strong binding of the ligand with the trichothecene 3-O-acetyltransferase, preventing as a result the acetylation of the trichothecene mycotoxin and destruction of the “self-defense mechanism” of theFusariumsp.


2017 ◽  
Vol 4 (23) ◽  
pp. 1700704 ◽  
Author(s):  
Yingzhi Jin ◽  
Zaifang Li ◽  
Leiqiang Qin ◽  
Xianjie Liu ◽  
Lin Mao ◽  
...  

2015 ◽  
Vol 31 (9) ◽  
pp. 1733-1740 ◽  
Author(s):  
Zhi-Jian. LIAO ◽  
◽  
Zhen-Li. QIN ◽  
Si-Nan. DU ◽  
Si-Yu. LI ◽  
...  

CrystEngComm ◽  
2021 ◽  
Author(s):  
wenjin zhang ◽  
Lingxiang Bao ◽  
Teng Fei ◽  
penghao lv ◽  
Si-Ping Pang ◽  
...  

A novel cocrystal explosive of CL-20/nitromethane in a 1:2 molar ratio is synthesised. Because of the CL-20 molecules were in the ε conformation in the cocrystal, it has a high...


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