[A new dihydrostilbene from aerial part of Cannabis sativa].

The present study investigated the chemical constituents in the aerial part of Cannabis sativa. The chemical constituents were isolated and purified by silica gel column chromatography and HPLC and identified according to their spectral data and physicochemical properties. Thirteen compounds were isolated from the acetic ether extract of C. sativa and identified as 3',5',4″,2-tetrahydroxy-4'-methoxy-3-methyl-3″-butenyl p-disubstituted benzene ethane(1), 16R-hydroxyoctadeca-9Z,12Z,14E-trienoic acid methyl ester(2),(1'R,2'R)-2'-(2-hydroxypropan-2-yl)-5'-methyl-4-pentyl-1',2',3',4'-tetrahydro-(1,1'-biphenyl)-2,6-diol(3), ß-sitosteryl-3-O-ß-D-glucopyranosyl-6'-O-palmitate(4), 9S,12S,13S-trihydroxy-10-octadecenoate methyl ester(5), benzyloxy-1-O-ß-D-glucopyranoside(6), phenylethyl-O-ß-D-glucopyranoside(7), 3Z-enol glucoside(8), α-cannabispiranol-4'-O-ß-D-glucopyranose(9), 9S,12S,13S-trihydroxyoctadeca-10E,15Z-dienoic acid(10), uracil(11), o-hydroxybenzoic acid(12), and 2'-O-methyladenosine(13). Compound 1 is a new compound, compound 3 is a new natural product, and compounds 2, 4-8, 10, and 13 were isolated from Cannabis plant for the first time.

A new dihydrostilbene from aerial part of Cannabis sativa / 中国中药杂志

The present study investigated the chemical constituents in the aerial part of Cannabis sativa. The chemical constituents were isolated and purified by silica gel column chromatography and HPLC and identified according to their spectral data and physicochemical properties. Thirteen compounds were isolated from the acetic ether extract of C. sativa and identified as 3',5',4″,2-tetrahydroxy-4'-methoxy-3-methyl-3″-butenyl p-disubstituted benzene ethane(1), 16R-hydroxyoctadeca-9Z,12Z,14E-trienoic acid methyl ester(2),(1'R,2'R)-2'-(2-hydroxypropan-2-yl)-5'-methyl-4-pentyl-1',2',3',4'-tetrahydro-(1,1'-biphenyl)-2,6-diol(3), β-sitosteryl-3-O-β-D-glucopyranosyl-6'-O-palmitate(4), 9S,12S,13S-trihydroxy-10-octadecenoate methyl ester(5), benzyloxy-1-O-β-D-glucopyranoside(6), phenylethyl-O-β-D-glucopyranoside(7), 3Z-enol glucoside(8), α-cannabispiranol-4'-O-β-D-glucopyranose(9), 9S,12S,13S-trihydroxyoctadeca-10E,15Z-dienoic acid(10), uracil(11), o-hydroxybenzoic acid(12), and 2'-O-methyladenosine(13). Compound 1 is a new compound, compound 3 is a new natural product, and compounds 2, 4-8, 10, and 13 were isolated from Cannabis plant for the first time.

Callus Culture of Scorzonera radiata as a New, Highly Productive and Stable Source of Caffeoylquinic Acids.

During our ongoing efforts to investigate biotechnological sources of caffeoylquinic acid (CQA) metabolites, we discovered the plant Scorzonera radiata Fisch. (Asteraceae), which is able to produce callus cultures with high yield and extremely high stability. An actively growing callus line, designated as Sr-L1, retained the ability to produce 11 CQAs during long-term cultivation (more than 20 years). A total of 29 polyphenolic compounds were identified in the leaves and Sr-L1 callus culture of S. radiata, including CQAs, lignol derivatives, flavonoids, and dihydrostilbenes. The composition of CQAs in the Sr-L1 culture was identical to that in the S. radiata leaves. Sr-L1 calli did not produce flavonoids and dihydrostilbenes, but produced lignol derivatives, which were absent in leaves. The HPLC-UV-HRMS determination showed the presence of monoacyl derivatives of CQAs such as 5-CQA, 4-CQA, cis-5-CQA, and 5-O-p-coumaroylquinic acid in the Sr-L1 culture. Among diacyl derivatives, 3,4-diCQA, 3,5-diCQA, cis-3,5-diCQA, 4,5-diCQA, 3-O-p-coumaroyl-5-O-CQA, and 3-O-caffeoyl-5-O-p-coumaroylquinic acid were found. The content of 5-CQA reached 7.54 mg/g dry weight and the content of 3,5-diCQA was as high as 18.52 mg/g dry weight. 3,5-diCQA has been reported to be of high nutritional and pharmacological value, as it alleviates inflammatory pain, reverses memory impairment by preventing neuronal apoptosis, and counteracts excessive adipose tissue expansion, serving as an attractive treatment option for obesity. The high content of 3,5-diCQA and the exceptional stability of biosynthesis make callus cultures of S. radiata a promising source for the development of drugs and nutraceuticals.

Characterization of prenylated phenolics in Glycyrrhiza uralensis by offline two-dimensional liquid chromatography/mass spectrometry coupled with mass defect filter.

Prenylated phenolics are an important class of natural products. In this study, an efficient strategy was established to systematically characterize the prenylated phenolics in Glycyrrhiza uralensis, a popular herbal medicine. Firstly, offline two-dimensional liquid chromatography/mass spectrometry (2DLC/MS) coupled with mass defect filter (MDF) technology was used to preliminarily detect 1631 potential prenylated phenolics. Secondly, the tandem mass spectrometry fragmentation features of different types of prenylated phenolics were investigated using 29 reference standards. Diagnostic fragmentations included neutral loss (NL) of 42 Da for the annular type and NL of 56 Da for the catenulate type in the positive ion mode, and NL of 56 Da for A-ring prenyl groups and NL of 69 Da for B-ring prenyl groups in the negative ion mode. As a result, the prenylation types, substitution sites, and adjacent OH and OCH3 substitutions of 320 prenylated phenolics in G. uralensis were rapidly characterized. Moreover, three prenylated dihydrostilbenes were purified from the aerial part of G. uralensis to verify the structural characterizations.

Dihydrostilbene glycosides from Camellia sinensis var. assamica and their cytotoxic activity.

Three undescribed dihydrostilbene glycosides, 3,5-dihydroxyldihydrostilbene 4'-O-[6''-O-(4'''-hydroxylbenzoyl)]-ß-D-glucopyranoside (1), 3,5-dihydroxyldihydrostilbene 4'-O-(6''-O-galloyl)-ß-D-glucopyranoside (2), and 3,5-dihydroxyldihydrostilbene 4'-O-[6''-O-(3''',4'''-dimethoxyl)galloyl]-ß-D-glucopyranoside (3), and seven known compounds, kaempferol 3-O-ß-D-glucopyranoside (4), isoquercitrin (5), kaempferol 3-O-α-L-rhamnoside (6), quercitrin (7), (6S,9R)-roseoside (8), (-)-epicatechin 3-O-gallate (9), and (-)-epigallocatechin 3-O-gallate (10) have been isolated from the methanol extract of the leaves of Camellia sinensis var. assamica (J.W.Mast.) Kitam. (synnonym of Camellia assamica (Mast.) H.T.Chang) (Theaceae). Their structures were elucidated by spectroscopic methods (1 D-, 2 D-NMR) and mass spectra. All compounds were evaluated for cytotoxic activity against human oral cancer (CAL27) and human breast cancer (MDAMB231) cell lines. Compound 10 showed significant cytotoxic activity against CAL27 and MDAMB231 cell lines with IC50 values of 9.78 ± 0.25 and 3.27 ± 0.18 µM, respectively, compared to those of positive control, capecitabine (IC50 values of 8.20 ± 0.75 and 5.20 ± 0.89 µM).

Xylochemical Synthesis and Biological Evaluation of Shancigusin C and Bletistrin G.

The biological activities of shancigusin C (1) and bletistrin G (2), natural products isolated from orchids, are reported along with their first total syntheses. The total synthesis of shancigusin C (1) was conducted by employing the Perkin reaction to forge the central stilbene core, whereas the synthesis of bletistrin G (2) was achieved by the Wittig olefination followed by several regioselective aromatic substitution reactions. Both syntheses were completed by applying only renewable starting materials according to the principles of xylochemistry. The cytotoxic properties of shancigusin C (1) and bletistrin G (2) against tumor cells suggest suitability as a starting point for further structural variation.

Two new phenylpropanoids and a new dihydrostilbenoid from the flower buds of Magnolia biondii pamp and their acetylcholinesterase inhibitory activities.

Two new phenylpropanoids, named (2'R*,3'R*)-2',3'-dihydroxy-4'-methoxy-caffeoyl butyrate (1), 9-acetoxy syringin (2), and a new dihydrostilbene, named (8'R)-4',5-dihydroxy-4,8'-dimethoxy-2-hydroxyethyl diphenylethane (3), together with five analogues (4-8), were isolated from the flower buds of Magnolia biondii Pamp. Their structures were elucidated by extensive spectroscopic analyses and comparison with literature data. The absolute configurations were deduced by comparison of experimental and calculated gauge-independent atomic orbital (GIAO) 1 D NMR data. Moreover, the isolated compounds (1-8) were evaluated in vitro for their acetylcholinesterase (AChE) inhibitory activities.

Dihydrostilbene glycosides from Camellia sasanqua and their α-glucosidase and α-amylase inhibitory activities.

Using chromatographic methods, three new dihydrostilbene glycosides, sasastilbosides A-C (1-3) and four known compounds, catechin (4), rutin (5), nicotiflorin (6), and rehmaionoside A (7) have been isolated from Camellia sasanqua Thunb. Their chemical structures were elucidated by spectroscopic methods (1 D-, 2 D-NMR) and mass spectra. Compounds 1-7 were evaluated for α-glucosidase and α-amylase inhibitory effects. Compounds 3 and 4 showed α-glucosidase inhibitory activity with IC50 values of 77.6 ± 1.6 and 72.4 ± 1.3 µM, respectively. Compound 1 showed α-amylase inhibitory activity with IC50 value of 53.7 ± 1.6 µM.

Dihydroxystilbenes prevent azoxymethane/dextran sulfate sodium-induced colon cancer by inhibiting colon cytokines, a chemokine, and programmed cell death-1 in C57BL/6J mice.

The incidence of colon cancer increased worldwide in 2019 and its treatment is urgent from a quality of life perspective. A relationship has been reported between elevated numbers of tumor-associated macrophages (TAMs) in the tumor microenvironment and a poor prognosis in cancer patients, and M2 TAMs have been shown to promote tumor growth by immunosuppression through the stimulation of programmed death-1 (PD-1, an immune check point receptor), interleukin (IL)-1ß, and monocyte chemoattractant protein (MCP)-1. We herein examined the effects of three synthetic dihydroxystilbenes (2,3-, 3,4-, and 4,4'-dihydroxystilbenes) on colon carcinogenesis, colon tumor growth, and colon cytokines (IL-1ß, IL-6, and tumor necrosis factor (TNF)-α), a chemokine (MCP-1), vascular endothelial growth factor (VEGF), and PD-1 levels in azoxymethane (AOM) plus dextran sulfate sodium (DSS)-treated C57BL/6J mice. The three dihydroxystilbenes inhibited colon carcinogenesis and tumor growth as well as increases in colon IL-1ß, IL-6, MCP-1, and PD-1 levels in AOM/DDS-treated mice (in vivo). The three dihydroxystilbenes also suppressed COX-2 expression in colon tumors (in vivo). The results obtained also revealed that the three dihydroxystilbenes inhibited PD-1 elevations in M2-THP-1 macrophages (in vitro). Therefore, the inhibition of AOM/DSS-induced colon carcinogenesis and colon tumor growth by 2,3-, 3,4-, and 4,4'-dihydroxystilbenes appears to be due to the suppression of M2 TAM differentiation and activation and PD-1 expression (immunosuppression) via reductions in COX-2 expression levels in the colon tumor microenvironment.

Cytotoxic Phenanthrene, Dihydrophenanthrene, and Dihydrostilbene Derivatives and Other Aromatic Compounds from Combretum laxum.

The chemical investigation of the roots and stems of Combretum laxum yielded a new dihydrostilbene derivative, 4'-hydroxy-3,3',4-trimethoxy-5-(3,4,5-trimethoxyphenoxy)-bibenzyl (1), two phenanthrenes (2-3), and three dihydrophenanthrenes (4-6), along with one lignan, three triterpenoids, one aurone, one flavone, one naphthoquinone, and two benzoic acid derivatives. Their structures were determined by 1D and 2D nuclear magnetic resonance (NMR) spectroscopic techniques and/or mass spectrometry data. The occurrence of dihydrostilbenoid, phenanthrene and dihydrophenanthrene derivatives is unprecedented in a Combretum species native to the American continent. 2,7-Dihydroxy-4,6-dimethoxyphenanthrene, 2,6-dihydroxy-4,7-dimethoxy-9,10-dihydrophenanthrene and 5-O-methyl apigenin are novel findings in the Combretaceae, as is the isolation of compounds belonging to the chemical classes of aurones and naphthoquinones, while (+)-syringaresinol is reported for the first time in the genus Combretum. Compounds 1-6 were also evaluated for their in vitro cytotoxicity against five human cancer cell lines, and radical-scavenging ability against 1,1-diphenyl-2-picryl-hydrazyl (DPPH). 6-Methoxycoelonin (4) was the most cytotoxic against melanoma cells (IC50 2.59 ± 0.11 µM), with a high selectivity index compared with its toxicity against nontumor mammalian cells (SI 25.1). Callosin (6), despite exhibiting the strongest DPPH-scavenging activity (IC50 17.7 ± 0.3 µM), proved marginally inhibitory to the five cancer cell lines tested, indicating that, at least for these cells, antioxidant potential is unrelated to antiproliferative activity.

Synthesis and evaluation of inhibitory activity in vitro of dihydrostilbenes against human neutrophil elastases.

Twelve dihydrostilbenes (including five new analogues) were prepared by the Witting-Hornor reaction from appropriate aromatic aldehydes and phosphonate esters, followed by hydrogenation in five steps. The in vitro inhibition activity against human neutrophil elastase (HNE) of these dihydrostilbenes was evaluated, and three 1,2-dihydroxylated dihydrostilbenes (6b, 6j, and 6l) exhibited stronger inhibitory activity against HNE than other analogues.