scholarly journals The Antimalarial Natural Product Salinipostin a Identifies Essential α/β Serine Hydrolases Involved in Lipid Metabolism in P. Falciparum Parasites

2019 ◽  
Author(s):  
Euna Yoo ◽  
Christopher J. Schulze ◽  
Barbara H. Stokes ◽  
Ouma Onguka ◽  
Tomas Yeo ◽  
...  
2019 ◽  
Author(s):  
Euna Yoo ◽  
Christopher J. Schulze ◽  
Barbara H. Stokes ◽  
Ouma Onguka ◽  
Tomas Yeo ◽  
...  

SUMMARYSalinipostin A (Sal A) is a potent antimalarial marine natural product with an undefined mechanism of action. Using a Sal A-derived activity-based probe, we identify its targets in the Plasmodium falciparum parasite. All of the identified proteins contain α/β serine hydrolase domains, and several are essential for parasite growth. One of the essential targets displays high homology to human monoacylglycerol lipase (MAGL) and is able to process lipid esters including a MAGL acylglyceride substrate. This Sal A target is inhibited by the anti-obesity drug Orlistat, which disrupts lipid metabolism and produces disorganized and stalled schizonts similar to Sal A. Resistance selections yielded parasites that showed only minor reductions in sensitivity and that acquired mutations in a protein linked to drug resistance in Toxoplasma gondii. This inability to evolve efficient resistance mechanisms combined with the non-essentiality of human homologs makes the serine hydrolases identified here promising antimalarial targets.


2020 ◽  
Vol 27 (2) ◽  
pp. 143-157.e5 ◽  
Author(s):  
Euna Yoo ◽  
Christopher J. Schulze ◽  
Barbara H. Stokes ◽  
Ouma Onguka ◽  
Tomas Yeo ◽  
...  

2019 ◽  
Vol 55 ◽  
pp. 296-304 ◽  
Author(s):  
Yunbing Shen ◽  
Shengnan Yang ◽  
Xueyan Hu ◽  
Man Zhang ◽  
Xiaoyao Ma ◽  
...  

Author(s):  
Sidney D. Kobernick ◽  
Edna A. Elfont ◽  
Neddra L. Brooks

This cytochemical study was designed to investigate early metabolic changes in the aortic wall that might lead to or accompany development of atherosclerotic plaques in rabbits. The hypothesis that the primary cellular alteration leading to plaque formation might be due to changes in either carbohydrate or lipid metabolism led to histochemical studies that showed elevation of G-6-Pase in atherosclerotic plaques of rabbit aorta. This observation initiated the present investigation to determine how early in plaque formation and in which cells this change could be observed.Male New Zealand white rabbits of approximately 2000 kg consumed normal diets or diets containing 0.25 or 1.0 gm of cholesterol per day for 10, 50 and 90 days. Aortas were injected jin situ with glutaraldehyde fixative and dissected out. The plaques were identified, isolated, minced and fixed for not more than 10 minutes. Incubation and postfixation proceeded as described by Leskes and co-workers.


Author(s):  
Ardalan A. Nabi ◽  
Lydia M. Scott ◽  
Daniel P. Furkert ◽  
Jonathan Sperry

The rare benzoxazepine ring in the alkaloid inducamide C is unstable and prone to rearrangement, indicating that structural revision of the natural product may be necessary.


2001 ◽  
Vol 120 (5) ◽  
pp. A546-A546
Author(s):  
D SWARTZBASILE ◽  
M GOLDBLATT ◽  
C SVATEK ◽  
M WALTERS ◽  
S CHOI ◽  
...  

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