Synthesis of sinomenine derivatives with potential anti-leukemia activity.

In recent years, with sinomenine hydrochloride as the main ingredient, Qingfengteng had been formulated as various dosage forms for clinical treatment. Subsequent findings confirmed a variety of biological roles for sinomenine. Here, 15 H2S-donating sinomenine derivatives were synthesized. Target hybrids a11 displayed substantial cytotoxic effects on cancer cell lines, particularly against K562 cells, with an IC50 value of 1.36 µM. In-depth studies demonstrated that a11 arrested cell cycle at G1 phase, induced apoptosis via both morphological changes in nucleus and membrane potential collapse in mitochondria. These results indicated a11 exerted an antiproliferative effect through apoptosis induction via mitochondrial pathway.

New aporphine alkaloids with antitumor activities from the roots of Thalictrum omeiense.

Two new aporphine alkaloids, 6aR-2'-(3-oxobutenyl)-thaliadin (1) and N-methylthalisopynine (2), along with ten known analogs (3-12), were isolated from the roots of Thalictrum omeiense W. T. Wang et S. H. Wang. Their structures were determined by extensive spectroscopic and X-ray crystallographic analyses. Compounds 1-7 and 9-12 were tested for their antiproliferative effects in vitro against two human cancer cell lines (A549 and MCF-7). Among them, compounds 1, 3, and 7 exhibited moderate inhibitory activity against the tested cell lines with IC50 values ranging from 23.73 to 34.97 µM.

[Lignans from stems and leaves of Cephalotaxus fortunei (â ¡)].

The present study aimed to explore the chemical constituents from the stems and leaves of Cephalotaxus fortunei. Seven lignans were isolated from the 75% ethanol extract of C. fortunei by various chromatographic methods, including silica gel, ODS column chromatography, and HPLC. The structures of the isolated compounds were elucidated according to physicochemical properties and spectral data. Compound 1 is a new lignan named cephalignan A. The known compounds were identified as 8-hydroxy-conidendrine(2), isolariciresinol(3), leptolepisol D(4), diarctigenin(5), dihydrodehydrodiconiferyl alcohol 9'-O-ß-D-glucopyranoside(6), and dihydrodehydrodiconiferyl alcohol 4-O-ß-D-glucopyranoside(7). Compounds 2 and 5 were isolated from the Cephalotaxus plant for the first time.

(±)-Pheharmines A-B, two pairs of racemic alkaloids with a morpholino[4,3,2-hi]ß-carboline core, from the roots of Peganum harmala.

Two pairs of unprecedented ß-carboline-phenylpropanoid heterogeneous alkaloids, (±)-pheharmines A-B (1-4), characterized by a morpholino[4,3,2-hi]ß-carboline core with two chiral centers, were isolated from the roots of Peganum harmala. The structures, including their absolute configurations, were identified using spectroscopic analyses and electronic circular dichroism (ECD) calculations. The biosynthetic hypothesis for the formation of pheharmines A-B was proposed. Compounds 1-4 exhibited moderate cytotoxic activities against HL-60 cell lines.

Cephalotaxine-type and homoerythrina-type alkaloids with antiproliferative effects from Cephalotaxus fortunei.

Twenty-two cephalotaxine-type and ten homoerythrina-type alkaloids, including seven previously undescribed ones, were isolated from the twigs and leaves and the seed kernels of Cephalotaxus fortunei. Their structures were established by spectroscopic analysis, single crystal X-ray diffraction, and ECD calculation methods. Cephalofortunine A ß-N-oxide (1) is the first nitrogen-oxidized homoerythrina-type alkaloid. The isolated compounds were evaluated for their in vitro antiproliferative effects against two human leukemia cell lines (THP-1 and K562). All compounds showed different levels of antiproliferation in THP-1 and K562 cells with GI50 values of 0.24-29.55 µM. Hainanensine (31) was the most active against two cancer cell lines with GI50 values of 0.24 ± 0.07, and 0.29 ± 0.01 µM, respectively.

[Isoquinoline alkaloids from two species of Thalictrum genus plants].

The chemical constituents from the roots of Thalictrum cultratum and T. baicalense were investigated. By various isolation methods, such as silica gel, aluminium oxide, ODS, and Sephadex LH-20 column chromatographies, and semi-preparative HPLC, 11 simple isoquinoline alkaloids were isolated from the ethanol extract of the roots of these two plants, including a new compound, named dehydrothalflavine(1), and ten known ones(2-11): N-methylcorydaline(2), N-methylthalidaldine(3), thaliflavine(4), oxyhydrastinine(5), noroxyhydrastinine(6), dimethoxyisoquinolone(7), thalactamine(8), dehydronoroxyhydrastinine(9), 6,7-dimethoxy-2-methyl-1,2,3,4-tetrahydroisoquinoline(10), and isopicnarrhine(11). Their structures were elucidated on the basis of HR-ESI-MS and 1 D and 2 D NMR techniques. Compound 1 was a new isoquinoline alkaloid. Compound 11 was obtained from Tha-lictrum plant for the first time. All compounds did not show cytotoxic activities against HL-60, U937, HCT116, Caco-2, and HepG2 cancer cell lines.

Polyprenylated xanthones from the twigs and leaves of Garcinia nujiangensis and their cytotoxic evaluation.

Inspired by the intriguing structures and bioactivities of polyprenylated xanthones, ten previously undescribed polyprenylated xanthones, nujiangxanthones G-P (1-10), and fifteen known ones (11-25) were isolated from the twigs and leaves of Garcinia nujiangensis. The structures of these compounds were established on the basis of spectroscopic data as well as comparison with the literature. Most of the isolates showed potent cytotoxicity against selected cancer cells. Compound 8 showed the highest effects against MDA-MB-231 and A549 cell lines with IC50 values of 4.12 and 2.67 µM and 16 demonstrated the most potent activity against MCF-7 cell line with an IC50 value of 3.36 µM.

Cytotoxic quinazoline alkaloids from the seeds of Peganum harmala.

Seventeen quinazoline alkaloids and derivatives, containing two pairs of new epimers, named as (S)- and (R)-1-(2-aminobenzyl)-3-hydroxypyrrolidin-2-one ß-d-glucopyranosyl-(1 → 6)-ß-d-glucopyranoside (1, 2), (S)- and (R)-vasicinone ß-d-glucopyranosyl-(1 → 6)-ß-d-glucopyranoside (3, 4), and a new enantiomer (12b), together with six known ones (5-8, 10, and 12a), and three pairs of known enantiomers (9, 11, and 13), were isolated from the ethanol extracts of the seeds of Peganum harmala L.. Their structures including the absolute configuration were elucidated by using 1D and 2D NMR, and ECD calculation approaches. The cytotoxic activities of all isolated compounds were evaluated. 11 showed moderate cytotoxicity against PC-3 cells with an IC50 value of 15.41 µM.

Bioassay- and Chemistry-Guided Isolation of Scalemic Caged Prenylxanthones from the Leaves of Garcinia bracteata.

With bioassay- and chemistry-guided fractionation, seven new caged prenylxanthones including two scalemic mixtures, epiisobractatin (1), 13-hydroxyisobractatin (2), 13-hydroxyepiisobractatin (3), 8-methoxy-8,8a-dihydrobractatin (4), 8-ethoxy-8,8a-dihydrobractatin (5), garcibracteatone (6), and 8-methoxy-8,8a-dihydroneobractiatin (7), and the eight known compounds 8-15 were isolated from the leaves of Garcinia bracteata. The structures were unambiguously elucidated through analysis of spectroscopic data. The 2D structures and relative configurations of 1 and 5 were confirmed by X-ray crystallographic analysis. The separation of the enantiomers of 1-5 was accomplished by chiral-phase HPLC. The absolute configurations of the enantiomers of 1 and 5 were assigned by comparison of the experimental and calculated electronic circular dichroism (ECD) spectra. The absolute configurations of the related compounds were determined via comparisons of their ECD data with those of the enantiomers of 1 and 5, respectively. Notably, compound 7, with a neo caged skeleton, is the first representative of a novel type of caged xanthone lacking a Δ8(8a) double bond. The isolated compounds exhibited significant cell growth inhibitory activities in vitro against human leukemic HL-60 and K562 cell lines, with GI50 values ranging from 0.2 to 8.8 µM. A preliminary structure-activity relationship is discussed.

Bioactive terpenoids from Silybum marianum and their suppression on NO release in LPS-induced BV-2 cells and interaction with iNOS.

Three new (1-3) and one known (4) bioactive terpenoids were isolated from the seeds of Silybum marianum based on the investigation to get new NO inhibitors. Their structures were determined by extensive NMR (1D and 2D NMR) and MS spectroscopic data, and the absolute configurations were identified by experimental and calculated ECD spectra. The NO inhibitory activities in murine microglial BV-2 cells and interactions with iNOS protein by molecular docking were evaluated for all compounds. The results showed that these compounds had potent NO inhibitory effects.

Neobraclactones A-C, three unprecedented chaise longue-shaped xanthones from Garcinia bracteata.

Neobraclactones A-C (1-3), featuring an unprecedented further rearranged prenylxanthone skeleton with a unique octahydro-2H-1,3-dioxacyclopenta[c,d]inden-2-one scaffold, along with their biosynthesis-related known compound neobractatin (4), were isolated from the leaves of Garcinia bracteata. Their structures with absolute configurations were determined by extensive analyses of spectroscopic data and ECD calculations. Compounds 1 and 2 showed significant growth inhibition activities against the human leukaemia HL-60 and K562 cell lines with GI50 values from 0.40 to 0.86 µM.

Antiproliferative Dimeric Aporphinoid Alkaloids from the Roots of Thalictrum cultratum.

Inspired by the intriguing structures and bioactivities of dimeric alkaloids, 11 new thalifaberine-type aporphine-benzylisoquinoline alkaloids, thalicultratines A-K, a tetrahydroprotoberberine-aporphine alkaloid, thalicultratine L, and five known ones were isolated from the roots of Thalictrum cultratum. Their structures were defined on the basis of NMR and HRESIMS data. The antiproliferative activities of compounds 1-17 were evaluated against human leukemia HL-60 and prostate cancer PC-3 cells. Most alkaloids showed potent cytotoxicity against selected cancer cells. Preliminary SARs are discussed. The most active new compound (3), with an IC50 value of 1.06 µM against HL-60 cells, was selected for mechanism of action studies. The results revealed that compound 3 induced apoptosis and arrested the HL-60 cell cycle at the S phase with the loss of mitochondria membrane potential. The nuclear morphological Hoechst 33258 staining assay was also carried out, and the results confirmed apoptosis.

Structurally Diverse Alkaloids from the Seeds of Peganum harmala.

Investigation of the alkaloids from Peganum harmala seeds yielded two pairs of unique racemic pyrroloindole alkaloids, (±)-peganines A-B (1-2); two rare thiazole derivatives, peganumals A-B (3-4); six new ß-carboline alkaloids, pegaharmines F-K (5-10); and 12 known analogues. Their structures, including stereochemistry, were elucidated through spectroscopic analyses, quantum chemistry calculations, and single-crystal X-ray diffraction. Notably, the incorporation of pyrrole and indole moieties in peganines A-B, thiazole fragments in peganumals A-B, and a C-1 α,ß-unsaturated ester motif in pegaharmine F (5) are all rare, and their presence in the genus Peganum were demonstrated for the first time. All isolates were tested for antiproliferative activities against the HL-60, PC-3, and SGC-7901 cancer cell lines, and compounds 9, 11, 12, and 13 exhibited moderate cytotoxicity against HL-60 cancer cell lines with IC50 values in the range of 4.36-9.25 µM.

ent-Abietane-type diterpenoids from the roots of Euphorbia ebracteolata with their inhibitory activities on LPS-induced NO production in RAW 264.7 macrophages.

Ten ent-abietane diterpenoids (1-10), including four new (1-4) and six known ones (5-10) were isolated from the roots of Euphorbia ebracteolata. Their structures were determined by 1D, 2D NMR, and HRESIMS. Compounds 2, 4, and 7 exhibited significant inhibitory activities on lipopolysaccharide (LPS)-induced nitric oxide production in RAW 264.7 macrophages with IC50 values of 0.69, 1.97, and 0.88µM, respectively. A primary structure-activity relationship was also discussed.

Antiproliferative activity and apoptosis inducing effects of nitric oxide donating derivatives of evodiamine.

The first series of nitric oxide donating derivatives of evodiamine were designed and prepared. NO releasing ability of all target derivatives was evaluated in BGC-823, Bel-7402 and L-02 cells. The cytotoxicity was evaluated against three human tumor cell lines (Bel-7402, A549 and BGC-823) and normal human liver cells L-02. The nitrate derivatives 11a and 11b only exhibited moderate activity and furoxan-based derivatives 13a-c, 14a and 14b showed promising activity. 13c showed good cytotoxic selectivity between tumor and normal liver cells and was further investigated for its apoptotic properties on human hepatocarcinoma Bel-7402 cells. The molecular mode of action revealed that 13c caused cell-cycle arrest at S phase and induced apoptosis in Bel-7402 cells through mitochondria-related caspase-dependent pathways.

Terpenoids from the Marine-Derived Fungus Aspergillus fumigatus YK-7.

Two new ß-bergamotane sesquiterpenoids, E-ß-trans-5,8,11-trihydroxybergamot-9-ene (1) and ß-trans-2ß,5,15-trihydroxybergamot-10-ene (2), were isolated from the marine-derived fungus Aspergillus fumigatus YK-7, along with three known terpenoids 3-5. Their structures were determined by spectroscopic methods (1D and 2D NMR, HR-ESI-MS). Antiproliferative effects on human leukemic monocyte lymphoma U937 and human prostate cancer PC-3 cell lines were measured in vitro. Compound 4 exhibited potent activity against the U937 cell line with an IC50 value of 4.2 µM.

Antiproliferative polycyclic polyprenylated acylphloroglucinols from Garcinia paucinervis.

Bioassay-guided isolation of the stems of Garcinia paucinervis led to one new adamantane-type polycyclic polyprenylated acylphloroglucinols (PPAPs), (-)-garpauvinin A (1), and four known analogues (2-5). The structure and absolute configuration of 1 was established via spectroscopic techniques and ECD method. All the isolates displayed moderate antiproliferative activity against HL-60, PC-3 and Caco-2 human cancer cell lines with IC50 values ranging from 0.81 to 19.92 µM, and exhibited low toxicity on WPMY-1 normal human cells, showing selectivity between normal and malignant prostate cells. The biosynthetic pathways of the isolated PPAPs were proposed.

Stilbenes with potent cytotoxicity from the seedcases of Paeonia suffruticosa Andrews.

Stilbenes (based on the 1,2-diphenylethylene skeleton) are a class of plant polyphenols with rich structural and bioactive diversity. Twenty-six stilbenes, including five undescribed compounds (7,8-dioxy-4,3',5'-trihydroxystilbene, trans-13'-methoxygnetin H, suffruticosol E, paestibenetrimerols A and B), were isolated from the seedcases of Paeonia suffruticosa Andrews. Their structures were elucidated by spectroscopic analyses and comparison with previously reported data. The absolute configurations of trans-13'-methoxygnetin H, suffruticosol E, paestibenetrimerols A and B were assigned from their respective electronic circular dichroism (ECD) spectra. Additionally, the structures of known compounds suffruticosols A, B and rockiol B were revised and the absolute configurations of them, and along with (+)-davidiol A, were also further determined by ECD. The isolated compounds, trans-gnetin H, cis-gnetin H and suffruticosol E, were found to have potent cytotoxicity against the DU-145 and MDA-MB-231 cell lines with IC50 values of 4.89-8.61 µM. The preliminary antitumor structure-activity relationship of these stilbenes is discussed as well.

Anti-tumor alkaloids from Peganum harmala.

Six alkaloids peharmalines F-K, along with 14 known ones, were isolated from the aerial part of Peganum harmala L.. The structures of the isolated compounds were determined based on their HR-ESI-MS data, extensive NMR spectroscopic analyses, and ECD calculations. 3-(4-Hydroxyphenyl)quinoline exhibited potent antiproliferative activity against the HepG-2 cell lines with an IC50 value of 3.05 µM. Norharmane displayed a moderate inhibition against A549 and HepG-2 cells with IC50 values of 16.45 µM and 17.27 µM, respectively.

New tirucallane-type triterpenoids from the resin of Boswellia carteriiand their NO inhibitory activities.

Six new tirucallane-type triterpenoids (1-6), along with ten known triterpenoids, were isolated from methylene chloride extract of the resin of Boswellia carterii Birdw. By the application of the comprehensive spectroscopic data, the structures of the compounds were clarified. The experimental electronic circular dichroism spectra were compared with those calculated, which allowed to assign the absolute configurations. Compounds 5 and 6 possesed a 2, 3-seco tirucallane-type triterpenoid skeleton, which were first reported. Their inhibitory activity against NO formation in LPS-activated BV-2 cells were evaluated. Compound 9 showed appreciable inhibitory effect, with an IC50 value of 7.58 ± 0.87 µmol·L-1.