Design, synthesis, and anti-triple negative breast cancer activity of novel Toosendanin derivatives.

Toosendanin (TSN) is a natural anti-cancer compound that is isolated from the traditional Chinese herbal Melia toosendan Sieb et Zucc. However, the research effect of TSN in the treatment of Triple negative breast cancer (TNBC) is still far from ideal. In this work, we investigated TSN and its derivatives in terms of their actions against MDA-MB-231 and HCC1806 TNBC cell lines. The results indicated that TSN and its derivative 11 showed excellent antitumor activity. Preliminary mechanistic studies showed that both compounds TSN and 11 induced S-phase arrest and G2/M phase cell number decrease in HCC1806 cells. Also, TSN and 11 significantly reduced the protein level of the well-known cancer suppressor gene p53, reduced the phosphorylation of AKT and ERK, and also induced the accumulation of phosphorylated p38 and p21.

The dichloromethane extract of Callicarpa longissima rich in diterpenoid phenols exerts anti-inflammatory effect via inhibiting the TLR4/NF-κB signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Callicarpa longissima is a typical Yao ethnomedicine that has been used to treat arthritis in China. Our previous study found that the dichloromethane extract (DCME) of C. longissima showed anti-inflammatory activity in vitro. However, the anti-inflammatory mechanism and detailed chemical composition of DCME remain unclear, which lead to the original interest of this study. AIM OF THE STUDY: The study aimed to evaluate the anti-inflammatory properties of the DCME from C. longissima and further explore the accurate chemical components responsible for this active extract. MATERIALS AND METHODS: The anti-inflammatory activity of DCME in vivo was tested with carrageenan-induced mice paw edema model. Its anti-inflammatory mechanism was explored with LPS-stimulated RAW264.7 macrophages model. The compounds in DCME were isolated by repeated column chromatography and their structures were identified on the basis of nuclear magnetic resonance spectroscopy. The anti-inflammatory activities of the isolates in vitro were also tested by suppressing releases of inflammatory mediators (NO, IL-6 and TNF-α) in RAW264.7 macrophages model. In addition, the molecular docking analysis, which evaluated the potential interaction between the compounds and Toll-like receptor 4 (TLR4) and nuclear factor κB (NF-κB), was performed. RESULTS: DCME effectively alleviated the mice paw edema induced by carrageenan. In LPS-stimulated RAW264.7 cells, DCME significantly decreased the production of interleukin (IL)-6 and tumor necrosis factor α (TNF-α) via inhibiting their mRNA transcription, down-regulated the expression of TLR4 and myeloid differentiation factor 88, inhibited the phosphorylation of alpha inhibitor of NF-κB (IκBα), NF-κB p65, and degradation of IκBα. Twelve diterpenoid phenols were identified from DCME, and they not only showed different inhibitory effects on the production of NO, IL-6 and TNF-α in LPS-stimulated RAW264.7 cells, but also could bind to TLR4 and NF-κB as analyzed by molecular docking. CONCLUSIONS: Taken together, DCME from C. longissima could inhibit inflammatory response both in vitro and in vivo, which is mainly attributed to the synergistic effect of abundant diterpenoid phenols through inhibiting the TLR4/NF-κB signaling pathway, and might be a promising agent for the treatment of inflammatory diseases.

seco-Prezizanne Sesquiterpenes and Prenylated C6-C3 Compounds from the Fruits of Illicium lanceolatum A. C. Smith.

Two new seco-prezizaane-type sesquiterpenes, 2ß-hydroxy-6-deoxyneoanisatin (1) and 3,4-anhydro-2-oxo-1α-hydroxy-6-deoxyneoanisatin (2), and two new prenylated C6 -C3 compounds, illilanceofunones A (3) and B (4), were obtained from the fruits of Illicium lanceolatum, along with four known prenylated C6 -C3 compounds (5-8). Their structures were proposed through HR-ESI-MS, 1 H, 13 C, and 2D NMR data interpretation. Moreover, the absolute configuration of 1 and 2 were further assigned by single-crystal X-ray diffraction analysis and electronic circular dichroism (ECD) calculations, respectively. Illihenryipyranol A (6) exhibited neuroprotective activity against MPP+ -induced PC12 cell damage in a dose-dependent manner.

Structure elucidation and anti-inflammatory mechanism of difengpienol C, a new neolignan isolated from Illicium difengpi.

Illicium difengpi is well-known as its stem barks that have been widely used in the Traditional Chinese Medicine (TCM) for therapy rheumatoid arthritis and traumatic injury. To comprehensive utilization of resources, the phytochemical investigation on the branches and leaves of this plant was carried out, which led to the isolation of an undescribed neolignan along with three known lignans. Their structures were elucidated on the basis of extensive spectroscopic data and the new compound was elucidated as a neolignan possessing a dihydropyran ring formed by a unique conjugation way and named difengpienol C. Difengpienol C showed the strongest anti-inflammatory activity in lipopolysaccharide (LPS)-stimulated RAW264.7 cells, which powerfully inhibited nitric oxide (NO), interleukin 6 (IL-6), tumor necrosis factor α (TNF-α) production and suppressed the mRNA transcription of inducible nitric oxide synthase (iNOS), IL-6 and TNF-α. Besides, difengpienol C blocked the activation of TLR4/MyD88/NF-κB signaling pathway. Therefore, difengpienol C might be a potent agent for anti-inflammatory drug development, and the non-traditional medicinal parts of Illicium difengpi can be identified as the source of natural anti-inflammatory molecules.

Preparative Isolation of Piceatannol Derivatives from Passion Fruit (Passiflora edulis) Seeds by High-Speed Countercurrent Chromatography Combined with High-Performance Liquid Chromatography and Screening for α-Glucosidase Inhibitory Activities.

Passiflora edulis Sims (passion fruit) seeds are often discarded as byproducts during juice processing. In fact, the seeds are of considerable commercial value in the food and cosmetics industry because of their rich polyphenols, especially piceatannol. In this study, high-speed countercurrent chromatography (HSCCC) was applied for the separation of stilbene polyphenols from passion fruit seeds. The n-hexane-ethyl acetate-methanol-water (1:2:1:2.8, v/v) was found to be the optimum two-phase solvent for the preparation of two major stilbenes, scirpusin B (8) and piceatannol (9) with purities of 90.2% and 94.8%, respectively. In addition, a continuous semipreparative HPLC was applied to further purify the HSCCC fractions containing minor stilbenes and obtain four new piceatannol derivatives (1-4) along with three known ones (5-7). The structures of these new compounds were determined using spectroscopic methods, including NMR, high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), and circular dichroism (CD). The isolated compounds were evaluated for α-glucosidase inhibitory activities in vitro. The result suggested that all of them exhibited more significant activity than acarbose, and passiflorinol B (2) had the strongest activity, with a IC50 value of 1.7 µM.

Phytochemical constituents of the pericarps of Illicium difengpi and their anti-inflammatory activity.

Phytochemical investigation on the pericarps of Illicium difengpi lead to the isolation and structure elucidation of a new sesquiterpene, sesquicaranoic acid C (1), a new neolignan, difengpiol C (2), and 10 known compounds. The structures and absolute configurations of two new compounds were determined by a combination of NMR and CD spectroscopic analyses. All isolates were evaluated for their inhibitory effects on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW264.7 cells.

[Exploration of objective quality evaluation parameter of Alismatis Rhizoma decoction pieces].

To establish a quality constant evaluation system of Alismatis Rhizoma decoction pieces,in order to provide reference for regulating the market circulation of this decoction pieces. A total of 18 batches of Alismatis Rhizoma decoction pieces were collected from different pharmaceutical factories,and the morphological parameters of each sample were tested. The content of alisol B 23-acetate in Alismatis Rhizoma decoction pieces was determined by HPLC in the 2015 edition of Chinese Pharmacopoeia,and the parameters such as quality constant and relative quality constant were calculated. The quality constant range of 18 batches of Alismatis Rhizoma decoction pieces was 0. 390-2. 076. If 18 batches of Alismatis Rhizoma decoction pieces were divided into 3 grades,taking 80% of the maximum quality constant as first grade,50% to 80% as second grade,and the rest as third grade,then the quality constant of firstgrade samples was ≥1. 66,the quality constant of second-grade samples was ≥1. 04 and <1. 66,and the quality constant of third-grade samples was <1. 04. The established quality constant evaluation method is objective and feasible,which can be used to classify the grade of Alismatis Rhizoma decoction pieces and provide a reference method to control the quality of this decoction pieces.

Lignan Glucosides from the Stem Barks of Illicium difengpi.

In this study, four new lignan glucosides, named difengpiosides A-D (1-4), were isolated from the stem barks of Illicium difengpi, together with seven known compounds 5-11. Their structures were identified on the basis of spectroscopic analyses (1D and 2D NMR, HRESIMS, CD) and a comparison with literature data. All the compounds were evaluated for their inhibitory effects on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW264.7 cells.

Vibsane-type diterpenes from leaves and twigs of Viburnum odoratissimum.

Seven new vibsane-type diterpenes, vibsanols C-H (1-6) and vibsanin X (7), together with seven analogues, were isolated from the leaves and twigs of Viburnum odoratissimum. The structures of the new compounds were elucidated by extensive spectroscopic methods. All the new compounds were detected for their cytotoxicity. Compound 1 showed significant cytotoxicity against all the tested cell lines (HL-60, SMMC-7721, A-594, MCF-7, and SW-480), with IC50 values of 3.35, 4.41, 5.18, 11.30, and 3.70 µM, respectively. Compounds 4 and 5 also displayed significant cytotoxicity against hepatocellular carcinoma SMMC-7721 cell line, with IC50 values of 3.69 and 3.52 µM, respectively.

[Studies on chemical constituents of Zhuang medicine Excoecaria venenata and their cytotoxic activity].

Fourteen compounds were isolated from 95% ethanol extract by silica gel, MCI, and ODS column chromatography. These compounds were respectively identified as quercetin (1), kaempferol (2), (+)-catechin (3), fraxin (4), protocatechuic acid (5), gallic acid (6), methyl gallate (7), ethyl gallate (8), apocynol A (9), baccatin (10), cerevisterol (11), ellagic acid (12), 3, 3',4'-tri-0-methylellagic acid(13) and N-benzoyl-L-phenylalaninyl-N-benzoyl-L-phenylalaninate(14) by analyzing their spectral data and comparing with the previously reported literatures. Except for gallic acid (6), all other compounds were isolated from this plant for the first time. Compounds 1, 2 and 6 showed moderate anti-proliferation activities on tumor cells.

Hupehenols A-E, selective 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) inhibitors from Viburnum hupehense.

Five selective 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) competitive inhibitors, hupehenols A-E (1-5), were isolated from Viburnum hupehense. The structure elucidation indicated that compounds 1-5 are new 20,21,22,23,24,25,26,27-octanordammarane triterpenoids. Their structures were established on the basis of NMR spectroscopic and mass spectrometric analysis. Hupehenols A-E (1-5) showed inhibition against human 11ß-HSD1, with hupehenols B (2) and E (5) having IC50 values of 15.3 and 34.0 nM, respectively. Moreover, hupehenols C (3) and D (4) are highly selective inhibitors of human 11ß-HSD1 when compared to murine 11ß-HSD1.

[Chemical constituents from EtOAc fraction of Sophora dunnii].

Sixteen compounds have been isolated from the EtOAc fraction of 95% ethanolic extract of Sophora dunnii through silica gel, Sephadex LH-20 and semi-prerarative HPLC column chromatographies. Their structures were identified on the basis of NMR and MS spectra data as phaseollidin (1), L-maackiain (2), 2-(2',4'-dihidroxyphenyl)-5,6-methylenedioxy benzofuran (3), 8-demethyl-farrerol (4), liquiritigenin (5), genistein (6), 6-methylgenistein (7), 5-O-methyl genistein (8), 7,2',4'-trihydroxys-5-methoxy-isoflavanone (9), 7, 3', 4'-trihydroxy-isoflavanone (10), erythribyssin D (11), calycosin (12), trans-resveratrol (13), cis-resveratrol (14), stigmasterol (15), ß-sitosterol (16). Among these, compounds 1-14 and 16 were isolated from this plant for the first time.

A new triterpenoid saponin from the root of Croton lachnocarpus Benth.

A new triterpenoid saponin, 3-O-ß-D-xylopyranosyl spathodic acid (1), was isolated from the EtOH extract of the root of Croton lachnocarpus Benth., together with four known compounds. These compounds were characterised on the basis of their spectral data and compatible with values in the literature. Compound 1 was the first triterpenoid glucoside isolated from the genus Croton. The known compound myriaboric acid (2) showed cytotoxic activity against human hepatocellular carcinoma SMMC-7721 cell line with an IC50 value of 42.2 µM.

A cytotoxic cardenolide and a saponin from the rhizomes of Tupistra chinensis.

A new cardenolide tupichinolide (1) and a new steroidal saponin tupichinin A (2), together with seven known compounds, were isolated from the rhizomes of Tupistra chinensis. Their structures were established using spectroscopic analysis and chemical methods. Compound 1 was the first cardenolide isolated from Tupistra chinensis and exhibited potent cytotoxicity against five human cancer cell lines: HL-60, SMMC-7721, A-549, MCF-7 and SW480.

Norditerpenoids from Salvia castanea Diels f. pubescens.

Three new norditerpenoids, castanol A-C (1-3), along with eighteen known diterpenoids, were isolated from Salvia castanea Diels f. pubescens. Their structures were elucidated by extensive spectroscopic analysis. All compounds were evaluated for their cytotoxic activities against five human cancer cell lines. The known compounds neo-tanshinlactone (12) and methyltanshinoate (17) exhibited significant cytotoxic activities against some cells.

Spirocyclic acylphloroglucinol derivatives from Hypericum beanii.

Four new acylphloroglucinols with an unusual 6/6/5 spirocyclic skeleton, hyperbeanols A-D (1-4), were isolated from the methanol extract of Hypericum beanii along with 16 known compounds. Their structures were established on the basis of spectroscopic and X-ray diffraction analysis. Hyperbeanols A-C were three stereoisomers different only at the relative configuration of C-4 and C-13, which were distinguished by the nuclear Overhauser effect spectroscopy (NOESY) spectroscopic data in combination with the single X-ray analysis of hyperbeanol A (1). The cytotoxic activity of hyperbeanols A-D against the cancer cell lines SK-BR-3, HL-60, SMMC-7721, PANC-1, MCF-7, and K562 was also evaluated.

Terpenoids and norlignans from Metasequoia glyptostroboides.

Four new terpenoids, metaseglyptorin A (1), metasequoic acid C (2), 12α-hydroxy-8,15-isopimaradien-18-oic acid (3), and (-)-acora-2,4(14),8-trien-15-oic acid (4), and three new norlignans, metasequirins D-F (5-7), were isolated from Metasequoia glyptostroboides, together with 15 known compounds. Structures of the new compounds were determined by analysis of their spectroscopic data, and the absolute configuration of 7 was established by the modified Mosher method. All of the compounds were evaluated for cytotoxicity against five human tumor cell lines.

Diterpenoid constituents of the roots of Salvia digitaloides.

Salvia digitaloides, belonging to the economically and medicinally important genus Salvia, is distributed in the northwest of Yunnan Province, People's Republic of China. The roots of this plant were soaked in alcohol by local Tibetans to make a special traditional "red wine", and many local people like to drink this traditional "red wine" to strengthen physical health. To investigate the bioactive diterpenoid constituents of the roots, a detailed phytochemical study was carried out, and 13 diterpenoids including two new norditerpenoids, dihydroneotanshinlactone (1) and 16,17-dinorpisferal A (2), were isolated. Their structures were established on the basis of detailed spectroscopic analysis. In addition, computational methods were applied to validate the stereochemistry of compound 1. For the bioassay to inhibit the growth of five tumor cell lines, neotanshinlactone (3) exhibited selective cytotoxic activity toward the human breast cancer cell line SK-BR-3, while the other four tanshinones (4-7) showed significant toxicity effects against all of the tested five cell lines.

Terpenoids from Salvia trijuga.

Nine new germacrane sesquiterpenes, trijugins A-I (1-9), a new lupane triterpenoid, 3alpha-O-acetyl-20(29)-lupen-2alpha-ol (10), and 24 known terpenoids were isolated from Salvia trijuga. The structure of compound 1 was confirmed by single-crystal X-ray diffraction. Compounds 1-10 and 32 were evaluated for their cytotoxicity against five human tumor cell lines. Compounds 9 and 32 exhibited moderate toxicity effects against several cell lines.

Polycyclic polyprenylated acylphloroglucinols and chromone O-glucosides from Hypericum henryi subsp. uraloides.

Two new C(30)-epimeric polycyclic polyprenylated acylphloroglucinols (PPAPs), named uralodins B and C (1 and 2, resp.), were isolated from the aerial parts of Hypericum henryi subsp. uraloides together with two new chromone glucosides, urachromones A and B (3 and 4, resp.), as well as 16 known compounds. Their structures were established by extensive NMR techniques and MS analysis. The epimers 1 and 2 always behaved like a single compound when examined by TLC, and were separated by HPLC. Their configuration was distinguished by comparative analysis of the NMR data with known analogues together with the ROESY experiment. All the isolated PPAPs were evaluated for their cytotoxic activities against HepG2, SGC7901, HL-60, and K562 cell lines. Compound 1 showed modest cytotoxic activities against SGC7901 and HL-60 cell lines, and 2 showed modest cytotoxic activities against HepG2, SGC7901, HL-60, and K562 cell lines.