Anti-Inflammatory and Cytotoxic Potential of New Phenanthrenoids from Luzula sylvatica

Abstract

Phenanthrenoids have been widely described, in the Juncaceae family, for their biological properties such as antitumor, anxiolytic, anti-microbial, spasmolytic, and anti-inflammatory activities. The Juncaceae family is known to contain a large variety of phenanthrenoids possessing especially anti-inflammatory and cytotoxic properties. Luzula sylvatica, a Juncaceae species, is widely present in the Auvergne region of France, but has never been studied neither for its phytochemical profile nor for its biological properties. We investigated the phytochemical profile and evaluated the potential anti-inflammatory activities of L. sylvatica aerial parts extracts. A bioassay-guided fractionation was carried out to identify the most active fractions. Nine compounds were isolated, one coumarin 1 and eight phenanthrene derivatives (2–9), including four new compounds (4, 5, 8 and 9), from n-hexane and CH2Cl2, fractions. Their structures were established by HRESIMS, 1D and 2D NMR experiments. The biological properties, especially the anti-inflammatory/antioxidant activities (ROS production) and antiproliferative activity on THP-1, a monocytic leukemia cell line, of each compound, were evaluated. Three phenanthrene derivatives 4, 6, and 7 showed very promising antiproliferative activities.

Unique Phenanthrenes from Juncus ensifolius and Their Antiproliferative and Synergistic Effects with the Conventional Anticancer Agent Doxorubicin against Human Cancer Cell Lines

“…The structure of the phenanthrene skeleton was assembled through 2D NMR analysis. It was concluded that the phenanthrene core of compound 2 is identical to sylvaticin A, a 9,10-dihydrophenanthrene recently described from Luzula sylvatica [ 27 ]. However, NMR characteristics of the H 2 -11 oxymethylene in 2 are different compared to those of sylvaticin A, including its upfield shifted carbon ( δ C 66.2 vs. 60.2) and magnetically inequivalent protons ( δ H 5.19 and 5.09, vs. δ H 5.01, 2H, s).…”

“…Analysis of the NMR spectra yielded a 9,10-dihydrophenanthrene skeleton containing a rare 10-OH group ( δ H10 5.10, 1H, br t, J = 2.9 Hz; δ c10 64.3). Comparison with literature data showed that ensifolin C is the 2-demethyl derivative of sylvaticin B, which was isolated from L. sylvatica [ 27 ]. The structure of compound 3 was therefore determined to be 2,10-dihydroxy-1,7-dimethyl-5-vinyl-9,10-dihydrophenanthrene.…”

“…Investigation of the compound on a chiral HPLC column resulted in only one peak. According to literature data on similar 10-hydroxyphenanthrenes, the configuration of C-10 can be assumed as ( S ) [ 27 , 28 ].…”

“…Besides the new compounds ensifolins A-M (1-13), four known phenanthrenes, namely, 2-hydroxy-1,7-dimethyl-5-vinyl-9,10-dihydrophenanthrene ( 14) [30], juncuenin B (15) [29], juncatrin B (16) [24], and sylvaticin A (17) [27], and 4-hydroxybenzaldehyde (18) and luteolin (19) were identified from J. ensifolius. The structural characterization was performed by means of HRESIMS and 1D and 2D NMR experiments and then by comparison of the 1 H and 13 C assignations with reported literature data.…”

Light regimen-induced variability of photosynthetic pigments and UV-B absorbing compounds in Luzula sylvatica from Arcto-Alpine tundra

“…Lower contents of Juncusol, Sylvaticin A, Sylvaticin C isomer 2, and Juncunol/Juncenil A were found in sun compared to shade leaves. Phenanthrenoid substances are reported from the plants of Juncaceae family (Tóth 2017) and L. sylvatica specifically (Gainche et al 2020). In these studies leaf type and category have not been taken into consideration.…”