Two new iridoid glycosides from the whole plant of Rehmania piasezkii.

Two new iridoid glycosides, piasezkiiosides A (1) and B (2), were isolated from aqueous extract of the whole plant of Rehmannia piasezkii. Their structures were established from the spectroscopic data, chemical transformation, and X-ray diffraction analysis. Compound 1 exhibited weak hepatoprotective activity against APAP-induced HepG2 cell damage.

Four new iridoid glycosides from the roots of Rehmannia glutinosa.

Four new iridoid glycosides (1-4), rehmaglutosides L-O, were isolated from the air-dried roots of Rehmannia glutinosa. Their structures were established from the spectroscopic data obtained and by chemical evidence. The known mellittoside (5) and ajugol (6) were also obtained in the current investigation, and the structure of mellittoside was unequivocally defined using X-ray diffraction data. Compounds 1-6 were tested for their cytotoxicity against five human tumor cell lines and proliferation effects on Lactobacillus Reuteri.

Seven new pentasaccharides from the roots of Rehmannia glutinosa.

Seven new pentasaccharides (1-7), rehmaglupentasaccharides A-G, were isolated from the air-dried roots of Rehmannia glutinosa. Their structures were established from the spectroscopic data obtained and by chemical evidence. The known verbascose (8) and stachyose (9) were also obtained in the current investigation, and the structure of stachyose was unequivocally defined using X-ray diffraction data. Compounds 1-9 were tested for their cytotoxicity against five human tumor cell lines, influence on dopamine receptor activation, and proliferation effects against Lactobacillus reuteri.

TRIP13 knockdown inhibits the proliferation, migration, invasion, and promotes apoptosis by suppressing PI3K/AKT signaling pathway in U2OS cells.

BACKGROUND: Although osteosarcoma (OS) is the most common malignant bone tumor, the biological mechanism underlying its incidence and improvement remains unclear. This study investigated early diagnosis and treatment objectives using bioinformatics strategies and performed experimental verification. METHODS AND RESULTS: The top 10 OS hub genes-CCNA2, CCNB1, AURKA, TRIP13, RFC4, DLGAP5, NDC80, CDC20, CDK1, and KIF20A-were screened using bioinformatics methods. TRIP13 was chosen for validation after reviewing literature. TRIP13 was shown to be substantially expressed in OS tissues and cells, according to Western blotting (WB) and quantitative real-time polymerase chain reaction data. Subsequently, TRIP13 knockdown enhanced apoptosis and decreased proliferation, migration, and invasion in U2OS cells, as validated by the cell counting kit-8 test, Hoechst 33,258 staining, wound healing assay, and WB. In addition, the levels of p-PI3K/PI3K and p-AKT/AKT in U2OS cells markedly decreased after TRIP13 knockdown. Culturing U2OS cells, in which TRIP13 expression was downregulated, in a medium supplemented with a PI3K/AKT inhibitor further reduced their proliferation, migration, and invasion and increased their apoptosis. CONCLUSIONS: TRIP13 knockdown reduced U2OS cell proliferation, migration, and invasion via a possible mechanism involving the PI3K/AKT signaling pathway.

Three new pyridine alkaloids and one new iridoid analogue from the leaves of Rehmannia glutinosa.

As part of an ongoing project on Rehmannia species, three new pyridine alkaloides (glutinosines A - C), and one new iridoid analogue (rehmaglutin E), were isolated from the leaves of Rehmannia glutinosa. The structures of the new compounds were established by extensive spectroscopic analysis and electronic circular dichroism calculations.

Four ionones and ionone glycosides from the whole plant of Rehmannia piasezkii.

Four new ionones and ionone glycosides (1-4) were isolated from the whole plant of Rehmannia piasezkii Maxim. Their planar structures as well as absolute configuration were confirmed via spectroscopic analysis, ECD calculation, and X-ray crystallography. Compounds 1-4 were tested for their cytotoxicity against five human tumor cell lines and ability to inhibit LPS-activated NO production in the BV2 cell line.

Synthesis and biological evaluation of new 2-methoxyestradiol derivatives: Potent inhibitors of angiogenesis and tubulin polymerization.

Here, we report the structural optimization of a hit natural compound, 2-ME2 (2-methoxyestradiol), which exhibited inhibitory activity but low potency on tubulin polymerization, anti- angiogenesis, MCF-7 proliferation and metastasis in vitro and in vivo. A novel series of 3,17-modified and 17-modified analogs of 2-ME2 were synthesized and investigated for their antiproliferative activity against MCF-7 and another five different human cancer cell lines leading to the discovery of 9i. 9i bind to tubulin colchicine site tightly, inhibited tubulin polymerization and disrupted cellular microtubule networks. Cellular mechanism studies revealed that 9i could induce G2/M phase arrest by down-regulated expression of p-Cdc2, P21 and cell apoptosis by regulating apoptosis-related proteins (Parp, Caspase families) in a dose-dependent manner. Importantly, 9i significantly inhibited HUVEC tube formation, proliferation, migration and invasion. The inhibitory effect against angiogenesis in vivo was confirmed by zebrafish xenograft. Furthermore, 9i could effectively inhibit the proliferation and metastasis of MCF-7 cells in vitro and in zebrafish xenograft. The satisfactory physicochemical property and metabolic stability of 9i further indicated that it can act as a promising and potent anti-angiogenesis, inhibiting proliferation and metastasis of breast cancer agent via targeting tubulin colchicine binding site.

Bioactive prenylated C6-C3 derivatives from the stems and leaves of Illicium fargesii.

Seventeen new prenylated C6-C3 derivatives, namely, illifargeins A-M (1-13), including three pairs of enantiomers (1, 5, and 12) and one norillifargeal A (14), together with eight known analogues (15-22), were isolated from the stems and leaves of Illicium fargesii. The structures of the new compounds were elucidated using spectroscopic data (UV, IR, 1D and 2D NMR, and HRESIMS). Their absolute configurations were determined by using experimental and calculated ECD data analysis, as well as a modified Mosher's method. Compounds 1a, 1b, 2, 3, 5a, 7, 10, 11, 15, 16, 19, and 20 showed potential activity against Coxsackie virus B3, with IC50 values ranging from 6.23 to 33.33 µM. Compounds 9 and 15 exhibited potential activity against influenza virus A, with IC50 values of 11.11 and 19.24 µM, respectively. Compounds 2, 3, and 18 exhibited potential anti-oxidant activity, with IC50 values ranging from 1.43 to 6.71 µM.

Bioactive bisbenzylisoquinoline alkaloids from the roots of Stephania tetrandra.

Ten new bisbenzylisoquinoline alkaloids (1-10) and eight known analogues (11-18) were obtained from the roots of Stephania tetrandra. The structures of these compounds were determined by spectroscopic methods, single-crystal X-ray diffraction, electronic circular dichroism analyses, and chemical method. Compounds 1, 15, and 16 showed the better anti-inflammatory activities with IC50 values of 15.26 ± 2.99, 6.12 ± 0.25, and 5.92 ± 1.89 µM, respectively. Compound 18 possessed cytotoxic activities against MCF-7, HCT-116, and HepG2 cell lines with IC50 values of 2.81 ± 0.06, 3.66 ± 0.26, and 2.85 ± 0.15 µM, respectively.

Increased CDKL3 expression predicts poor prognosis and enhances malignant phenotypes in esophageal squamous cell carcinoma.

BACKGROUND: Cyclin-dependent kinase-like 3 (CDKL3) is a putative protein serine kinase and plays an important role in the regulation of cell growth and/or differentiation. However, studies on the function of CDKL3 in esophageal squamous cell carcinoma (ESCC) is limited. In our study, we explored the role and prognosis of CDKL3 in ESCC and underlying mechanism. MATERIALS AND METHODS: The expression of CDKL3 was investigated by quantitative reverse transcription polymerase chain reaction and immunohistochemical staining. CDKL3 expression was downregulated by the RNAi-mediated knockdown. The functions of CDKL3 on cell growth were assessed by Celigo image cytometry, MTT assay, cell-cycle analysis, Annexin V assay, and caspase-3/7 activity analysis. The effect of CDKL3 on cellular invasive was investigated by the Transwell assay. Pathscan Stress Signaling Antibody Array was used to study the underlying mechanism. Additionally, the association between the survival and CDKL3 expression in ESCC were evaluated based on the TCGA data. RESULTS: CDKL3 was highly expressed in ESCC tissues and cell lines. TE-1 cells transfected with CDKL3-shRNA-lentivirus significantly decreased CDKL3 expression and resulted in inhibiting cell proliferation, inducing the S-phase cell-cycle arrest, attenuating cellular invasive and increasing cell apoptosis. The expression of pERK1/2, p-Akt, p-Smad2, p-p38 mitogen-activated protein kinase, cleaved caspase-7, and phospho-Chk1 were significantly decreased by CDKL3 knockdown. In addition, high expression of CDKL3 was associated with shorter overall survival. CONCLUSION: Our findings suggest that higher expression of CDKL3 is correlated with poor prognosis in patients with ESCC and play a vital role in the malignant phenotype of ESCC cell lines, which indicating that CDKL3 may be as a new therapeutic target in ESCC.

Iridal-Type Triterpenoids with a Cyclopentane Unit from the Rhizomes of Belamcanda chinensis.

Ten new iridal-type triterpenoid derivatives, polycycloiridals K-T (1-10), with a cyclopentane moiety originating from the cyclization of the homofarnesyl side chain were isolated from the rhizomes of Belamcanda chinensis. Their structures were established by spectroscopic data, a single-crystal X-ray diffraction analysis, TDDFT quantum mechanical calculations, and chemical derivatization. Compounds 2 and 10 exhibited 33.4% and 32.9% inhibitory activities, respectively, against PTP1b (protein tyrosine phosphatase) at a concentration of 10 µM. A putative biosynthetic pathway is proposed.

New iridal-type triterpenoid derivatives with cytotoxic activities from Belamcanda chinensis.

Eight new iridal-type triterpenoid derivatives, including two noriridals with ether bridge (1-2); two iridals lactone (3-4), four monocyclic iridals (5-8), together with five known iridals (9-14) were identified from the rhizome of Belamcanda chinensis. Their structures were elucidated on the basis of comprehensive spectroscopic methods and electronic circular dichroism (ECD) calculations. Bioassay results showed that belamcanoxide B (1) exhibited moderated cytotoxic activities against HCT-116 and MCF-7 cell lines with IC50 values of 5.58 and 3.35 µM.

Two new iridal-type triterpenoids from Iris forrestii.

Two new iridal-type triterpenoids, named forrestins A and B (1 and 2), were isolated from Iris forrestii Dykes by comprehensive chromatographic methods. The structures of 1 and 2 were elucidated by interpretation of extensive spectroscopic data including 1D and 2D NMR and HRESIMS.

Nine new compounds from the whole plants of Rehmannia henryi.

Eight new iridoids (1-8) and an ionone glucoside (9), together with 31 known compounds (10-40), were isolated from the whole plants of Rehmannia henryi. The structures of these compounds were elucidated on the basis of their spectroscopic data and chemical evidence.

Five new iridoids from the whole plants of Rehmannia henryi.

Five new iridoids (1-5), jiohenrins A-E, together with sixteen known compounds (6-21), were isolated from the whole plants of Rehmannia henryi. The structures of these compounds were elucidated on the basis of their spectroscopic data.

Secoheliosphanes A and B and Secoheliospholane A, Three Diterpenoids with Unusual seco-Jatrophane and seco-Jatropholane Skeletons from Euphorbia helioscopia.

Secoheliosphanes A (1) and B (2) and secoheliospholane A (3), possessing an unusual 7,8-seco-jatrophane skeleton and an unprecedented 9,10-seco-7,10-epoxyjatropholane skeleton, respectively, were isolated from the whole plants of Euphorbia helioscopia, along with two biogenetically precursors, a new jatrophane diterpene, 2-epi-euphornin I (4) and a known jatrophane diterpene, euphoscopin A (5). Structures of 1-4 including absolute configurations were elucidated on the basis of spectroscopic data, X-ray crystallography, and chemical conversion. Compounds 1 and 2 were prepared from 4 and 5, respectively, confirming their structural assignments. Notably, 1 and 2 presented the first examples of seco-jatrophane-type diterpenoids and 3 featured a novel 5/6/7/7-fused tetracyclic ring skeleton. Among them, compound 2 showed modest activity against HSV-1 with IC50 value of 6.41 µM.

Belamchinenin A, an unprecedented tricyclic-fused triterpenoid with cytotoxicity from Belamcanda chinensis.

Belamchinenin A (1), an unprecedented 6/5/6-fused tricyclic triterpenoid with a novel carbon skeleton, has been isolated from the rhizomes of Belamcanda chinensis. Compound 1 features a half-caged tricyclic nucleus with a flexible geranyl side chain. Its structure was determined by the interpretation of spectroscopic data. The absolute configuration of tricyclic nucleus system of 1 was unequivocally assigned by ECD calculation. Geometries optimization indicated that the tricyclic nucleus system is rigid. Compound 1 showed cytotoxic activities against five cells with IC50 values from 2.29 to 4.47 µM.

A Chemical Investigation of the Leaves of Morus alba L.

The leaves of Morus alba L. are an important herbal medicine in Asia. The systematic isolation of the metabolites of the leaves of Morus alba L. was achieved using a combination of liquid chromatography techniques. The structures were elucidated by spectroscopic data analysis and the absolute configuration was determined based on electronic circular dichroism (ECD) spectroscopic data and hydrolysis experiments. Their biological activity was evaluated using different biological assays, such as the assessment of their capacity to inhibit the aldose reductase enzyme; the determination of their cytotoxic activity and the evaluation of their neuroprotective effects against the deprivation of serum or against the presence of nicouline. Chemical investigation of the leaves of Morus alba L. resulted in four new structures 1⁻4 and a known molecule 5. Compounds 2 and 5 inhibited aldose reductase with IC50 values of 4.33 µM and 6.0 µM compared with the potent AR inhibitor epalrestat (IC50 1.88 × 10−3 µM). Pretreatment with compound 3 decreased PC12 cell apoptosis subsequent serum deprivation condition and pretreatment with compound 5 decreased nicouline-induced PC12 cell apoptosis as compared with control cells (p < 0.001).

Polycycloiridals with a Cyclopentane Ring from Iris tectorum.

Six new iridal-type triterpenoids containing an unprecedented cyclopentane ring, polycycloiridals E-J (1-6), were isolated from a large-scale re-extraction of Iris tectorum. A possible biosynthesis pathway is postulated. The known spirioiridotectal D (7) was also obtained in the current investigation, and its structure was unequivocally defined using X-ray diffraction data. Compound 7 suppressed LPS-activated NO production in the BV2 cell line with an IC50 value of 0.54 µM.

Three new triterpenoids from Ganoderma theaecolum.

Three new triterpenoids (1-3), together with four known triterpenoids (4-7), were isolated from the fruiting bodies of Ganoderma theaecolum. Their structures were elucidated on the basis of their spectroscopic data and chemical evidence. Compounds 4 and 6 exhibited antitumor activities against H460 cells with IC50 values of 22.4 and 43.1 µM, respectively. And the cytotoxic activities of compounds 4 and 5 against MDA-MB-231 cancer cell lines were assayed with IC50 values of 49.1 and 75.8 µM, respectively.