1,2-Didehydrotanshinone IIA

Selective in vitro and in silico butyrylcholinesterase inhibitory activity of diterpenes and rosmarinic acid isolated from Perovskia atriplicifolia Benth. and Salvia glutinosa L.[Pubmed:27817931]

Phytochemistry. 2017 Jan;133:33-44.

Cholinesterase inhibition is one of the most treatment strategies against Alzheimer's disease (AD) where metal accumulation is also strongly associated with pathology of the disease. In the current study, we assessed inhibitory effect against acetyl- (AChE) and butyrylcholinesterase (BChE) and metal-chelating capacity of twelve diterpenes: arucadiol, miltirone, tanshinone IIa, 1-oxomiltirone, cryptotanshinone, 1,2-didehydromiltirone, 1,2-Didehydrotanshinone IIA, 1beta-hydroxycryptotanshinone, 15,16-dihydrotanshinone, tanshinone I, isotanshinone II, 1(S)-hydroxytanshinone IIa, and rosmarinic acid, isolated from Perovskia atriplicifolia and Salvia glutinosa. The compounds were tested at 10 mug/mL using ELISA microtiter assays against AChE and BChE. QSAR and molecular docking studies have been also performed on the active compounds. All of the compounds showed higher [e.g., IC50 = 1.12 +/- 0.07 mug/mL for 1,2-didehydromiltirone, IC50 = 1.15 +/- 0.07 mug/mL for cryptotanshinone, IC50 = 1.20 +/- 0.03 mug/mL for arucadiol, etc.)] or closer [1,2-Didehydrotanshinone IIA (IC50 = 5.98 +/- 0.49 mug/mL) and 1(S)-hydroxytanshinone IIa (IC50 = 5.71 +/- 0.27 mug/mL)] inhibition against BChE as compared to that of galanthamine (IC50 = 12.56 +/- 0.37 mug/mL), whereas only 15,16-dihydrotanshinone moderately inhibited AChE (65.17 +/- 1.39%). 1,2-Didehydrotanshinone IIA (48.94 +/- 0.26%) and 1(S)-hydroxytanshinone IIa (47.18 +/- 5.10%) possessed the highest metal-chelation capacity. The present study affords an evidence for the fact that selective BChE inhibitors should be further investigated as promising candidate molecules for AD therapy.

Isolation and Fast Selective Determination of Nor-abietanoid Diterpenoids from Perovskia atriplicifolia Roots Using LC-ESI-MS/MS with Multiple Reaction Monitoring.[Pubmed:26410997]

Nat Prod Commun. 2015 Jul;10(7):1149-52.

In the first part of this study we extracted, isolated, and identified the main diterpenoid constituents from the roots of a Central Asian medicinal and ornamental plant--Perovskia atriplicifolia Benth. Eight major nor-abietanoid pigments were obtained using NP silica gel column chromatography and preparative RP-HPLC: cryptotanshinone, 1-hydroxycryptotanhinone, miltirone, 1-oxomiltirone, tanshinone IIa, 1,2 didehydrotanshinone IIa, 1,2 didehydromiltirone, the non-quinone diterpenoid - arucadiol, as well as rosmarinic acid as a main phenolic compound. Secondly, we used the obtained compounds for fast and selective determination of the main diterpenes present in P. atriplicifolia root extract. After extraction with n-hexane, the quantitative analysis was carried out by LC-MS/MS with a triple quadrupole (qQq) mass detector without any prior clean-up step. Identification of the diterpenes was confirmed by multiple reaction monitoring (MRM) using the most representative transitions from the precursor ions, while the most sensitive transitions were used for quantification in a 19-minute run. Most of the isolated and analyzed compounds had not been previously reported from this species. This easily cultivated plant is a promising source of several pharmacologically valuable abietanoid diterpenoids.