2. Academic Validation
  3. Norditerpenoids with Selective Anti-Cholinesterase Activity from the Roots of Perovskia atriplicifolia Benth

Norditerpenoids with Selective Anti-Cholinesterase Activity from the Roots of Perovskia atriplicifolia Benth

  • Int J Mol Sci. 2020 Jun 23;21(12):4475. doi: 10.3390/ijms21124475.
Sylwester Ślusarczyk 1,  F Sezer Senol Deniz 2,  Renata Abel 1 3,  Łukasz Pecio 4,  Horacio Pérez-Sánchez 5,  José P Cerón-Carrasco 6,  Helena den-Haan 5,  Priyanka Banerjee 3,  Robert Preissner 3,  Edward Krzyżak 7,  Wiesław Oleszek 4,  Ilkay E Orhan 2,  Adam Matkowski 1
Affiliations

Affiliations

  • 1 Department of Pharmaceutical Biology and Botany, Wroclaw Medical University, 50556 Wroclaw, Poland.
  • 2 Department of Pharmacognosy, Faculty of Pharmacy, Gazi University, 06330 Ankara, Turkey.
  • 3 Structural Bioinformatics Group, Institute for Physiology & ECRC, Charité University Medicine, 10115 Berlin, Germany.
  • 4 Department of Biochemistry and Crop Quality, IUNG-Institute of Soil Science and Plant Cultivation, 24100 Puławy, Poland.
  • 5 Structural Bioinformatics and High Performance Computing Research Group, Universidad Católica San Antonio de Murcia (UCAM), 30107, Murcia, Spain.
  • 6 Reconocimiento y Encapsulación Molecular (REM), Universidad Católica San Antonio de Murcia (UCAM), 30107 Murcia, Spain.
  • 7 Department of Inorganic Chemistry, Wroclaw Medical University, 50556 Wroclaw, Poland.
PMID: 32586060 DOI: 10.3390/ijms21124475
Abstract

Inhibition of cholinesterases remains one of a few available treatment strategies for neurodegenerative dementias such as Alzheimer's disease and related conditions. The current study was inspired by previous data on anticholinesterase properties of Diterpenoids from Perovskia atriplicifolia and Other Lamiaceae species. The acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibition by the three new natural compounds-(1R,15R)-1-acetoxycryptotanshinone (1), (1R)-1-acetoxytanshinone IIA (2), and (15R)-1-oxoaegyptinone A (3)-as well as, new for this genus, isograndifoliol (4) were assessed. Three of these compounds exhibited profound inhibition of butyrylcholinesterase (BChE) and much weaker inhibition of acetylcholinesterase (AChE). All compounds (1-4) selectively inhibited BChE (IC50 = 2.4, 7.9, 50.8, and 0.9 µM, respectively), whereas only compounds 3 and 4 moderately inhibited AChE (IC50 329.8 µM and 342.9 µM). Molecular docking and in silico toxicology prediction studies were also performed on the active compounds. Natural oxygenated norditerpenoids from the traditional Central Asian medicinal plant P. atriplicifolia are selective BChE inhibitors. Their high potential makes them useful candidate molecules for further investigation as lead compounds in the development of a natural drug against dementia caused by neurodegenerative diseases.

Keywords

cholinesterases; molecular docking; structure elucidation; tanshinones.

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