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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.

Two new dimers of ambuic acid, pestaloversicoloric acids A (

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 IC

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.

Baicalensines A (1) and B (2) were isolated from the roots of Thalictrum baicalense and structurally characterized using spectroscopic data, 13C NMR calculations, and the CASE algorithm. Compound 1, representing a new class of alkaloid dimers, contains berberine conjugated to a ring-opened isoquinoline. Compound 2 is the first reported natural benzylisoquinoline bearing a formyl group at C-3. Plausible biosynthetic pathways are proposed. Compound 1 exerted moderate cytotoxicity against the Caco-2 and HL-60 cell lines.

Two new dimers of ambuic acid, pestaloversicoloric acids A (1) and B (2), and a known derivative, 13(S)-hydroxyambuic acid (3), were isolated from the static fermentation product of Pestalotiopsis versicolor. The structural identification was accomplished via analyses on the data of HR-MS, 1 D and 2 D NMR, and ECD. Different from the well-known exo-type dimer, torreyanic acid, compounds 1 and 2 represent the first example of endo-type product derived from the intermolecular Diels-Alder reaction of two molecules of ambuic acid derivative with the identical absolute stereochemistry.

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.

Background The simple and caged xanthones from Clusiaceae showed significant antineoplastic activity. This study aims to identify structural diverse xanthones and search for novel antitumor natural products from this family plants. Methods The structures of new compounds 1a and 1b were elucidated mainly through comprehensive NMR and MS spectroscopic data, and their absolute configurations were determined by the comparison of the experimental and calculated electronic circular dichroism. Results A pair of new xanthone enantiomers, (+)- and (−)-cracochinxanthone A (1a and 1b), along with thirty known analogues (2–31), were isolated from extracts of the stems and leaves of C. cochinchinense. Preliminary biological assay of some isolates against HL-60, PC-3, and MDA-MB-231 cancer cell lines. Conclusion Some isolated xanthones exhibited high sensitivity against three human malignant cell lines and the structure–activity relationship study showed that the prenyl and geranyl units may play an important role in antitumor activity.

In this study, we combined two enemin-type diterpenoid derivatives with two well-established hydrogen sulfide moieties via ester or different anhydride linkers, to search apoptosis inducing drug candidate capable of hydrogen sulfide generating. Therefore, a series of hybrids were synthesized and superior antiproliferative efficacy accompanied with enhanced selectivity was observed under extensive pharmacological evaluations. A standard methylene blue (MB+) method was applied to measure the capacity for the hydrogen sulfide generation of all the target derivatives. One particular molecule A1, which contained α-thioctic acid moiety for hydrogen sulfide donating, manifested more potent antiproliferative activity. It exerted inhibitory effects against Bel-7402, SGC-7901 and A549 cell lines with IC50 values of 2.16, 5.07 and 6.98 μM respectively. While it exacted relatively low effects over human normal cell lines L-02 and PBMC with IC50 values of 15.81 μM for the prior and 14.15 μM for the latter, and displayed better selectivity index (SI) than parent diterpenoids. A high dosage of H2S release was also recorded. Hence, A1 was most suitable for mechanistic exploration on account of both safety and efficacy. The ensuing biological assays revealed central role of apoptosis in A1’s mode of action for antiproliferative efficacy, which led to further confirmation of G1 phase cell cycle arrest, mitochondria membrane potential collapse and apoptotic activation in Bel-7402 cells. Further western blot assay on intrinsic mitochondria pathway unlocked intricate interplay among a series of apoptotic related proteins in which Bax, caspase-3 and cytochrome c went through up-regulation, while Bcl-2, Bcl-xL and procaspase-3 undergone down-regulation. In a nutshell, a hydrogen sulfide releasing hybrid A1 was synthesized and antiproliferative evaluation identified it to be a worthy drug candidate for future in depth study.

Four tyrosine-derived spiro-isoxazoline analogues, including two new ones (3–4), were isolated from the flowers of Xanthoceras sorbifolia Bunge. The planar structures and the conformations were established by the analyses of the 1D and 2D NMR spectroscopic data, and the absolute configuration of compound 4 was determined via ECD calculation by time-dependent density functional theory (TDDFT). The biosynthetic pathway involving oxidative cyclization of the aldoxime precursor and the substrate-selective reduction reaction was proposed for these four spiro-isoxazolines. Additionally, compounds 1–4 did not exhibit inhibitory effect against the angiogenesis of intersegmental vessels of zebrafish embryo.

Nitroreductase is a reductase that catalyzes nitro aromatic compounds to aromatic amines. It effectively reduces nitro to hydroxylamine or amino when in the presence of nicotinamide adenine dinucleotide or nicotinamide adenine dinucleotide phosphate. In terms of tumor, nitroreductase is upregulated in hypoxic tumor cells, and its content is directly related to the degree of hypoxia. Therefore, effective detection of nitroreductase is important not only for the study of cellular hypoxia, but also for the diagnosis and treatment of tumors and related diseases. In this review, we summarized the latest advances in small-molecule fluorescent probes for nitroreductase detection based on different fluorescence mechanisms, with a focus on research conducted between May 2018 and December 2020. The development trends and application prospect in this rapidly developing field were also highlighted.

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 IC

Marine natural products are known for their diverse chemical structures and extensive bioactivities. Renieramycins, the member of tetrahydroisoquinoline family of marine natural products, arouse interests because of their strong antitumor activities and similar structures to the first marine antitumor agent ecteinascidin-743, approved by the European Union. According to the literatures, researches on the pharmacological activities of renieramycins mainly focus on their antitumor activities. In addition, by structural modification, derivatives of renieramycins show stronger antiproliferative activity and less accidental necrosis activity on cells. Nevertheless, the difficulties in extraction and separation hinder their further development. Hence, the synthetic chemistry work of renieramycins plays a key role in their further development. In this review, currently reported researches on the synthetic chemistry, pharmacological activities and structural modification of renieramycins are summarized, which will benefit future drug development and innovation.

Baicalensines A (

Hydrogen sulfide (H2S) is considered as a novel second-messenger molecule associated with the modulation of various physiological and pathological processes. In the field of antitumor research, endogenous H2S induces angiogenesis, accelerates the cell cycle and inhibits apoptosis, which results in promoting oncogenesis eventually. Interestingly, high concentrations of exogenous H2S liberated from donors suppress the growth of various tumors via inducing cellular acidification and modulating several signaling pathways involved in cell cycle regulation, proliferation, apoptosis and metastasis. The selective release of certain concentrations of H2S from H2S donors in the target has been considered as an alternative tumor therapy strategy. Triple-negative breast cancer (TNBC), an aggressive subtype with less than one year median survival time, is known to account for approximately 15–20% of all breast cancers. Due to the lack of approved targeted therapy, the clinical treatment of TNBC is still hindered by metastasis as well as recurrence. Significant efforts have been spent on developing novel treatments of TNBC, and remarkable progress in the control of TNBC by H2S donors and their derivatives have been made in recent years. This review summarizes various pathways involved in antitumor and anti-metastasis effects of H2S donors and their derivatives on TNBC, which provides novel insights for TNBC treatment.

A series of furoxan derivatives of chromone were prepared. The antiproliferative activities were tested against five cancer cell lines HepG2, MCF-7, HCT-116, B16, and K562, and two normal human cell lines L-02 and PBMCs. Among them, compound 15a exhibited the most potent antiproliferative activity. It was also found 15a produced more than 8 µM of NO at the peak time of 45 min by Griess assay. Generally, antiproliferative activity is positively related to NO release to some extent. Further in-depth studies on apoptosis-related mechanisms showed that 15a caused S-phase cell cycle arrest in a concentration-dependent manner and induced apoptosis significantly through mitochondria-related pathways. Human apoptosis protein array assay also demonstrated 15a increased the expression levels of pro-apoptotic Bax, Bad, HtrA2 and Trail R2/DR5. The expression of catalase and cell cycle blocker claspin were similarly up-regulated. In balance, 15a induced K562 cells death through both endogenous and exogenous pathways., Graphical Abstract

Ten new flavone 8-C-glucosides, trollichinensides A–J, with the substitution of various acyls at C-2″, C-3″, or C-6″ of the glucose moiety, together with thirteen known ones were isolated from the flowers of Trollius chinensis. Spectroscopic analyses including NMR and HRESIMS resulted in the establishment of the structures of these constituents and electronic circular dichroism (ECD) experiment was employed for the determination of the absolute configuration of the glucose residue in these molecules.

Bioassay-guided fractionation of the dichloromethane-soluble portion of the stems of Garcinia paucinervis led to the isolation of eight new xanthones, including three pairs of enantiomers, (+) and (−) paucinervins L-N (1a-3a, and 1b-3b), one optically pure compound, (−) paucinervin O (4), and one new analogue, paucinervin P (5), as well as thirteen known xanthones (6–18). Their structures were established by detailed analysis of extensive spectroscopic data. The absolute configurations of 1–4 were confirmed by ECD calculations. All the isolates 1–18 displayed antiproliferative effect against HL-60 with IC50 values ranging from 0.87 to 29.14 μM, of which compound 5 was the most active. Compounds 6, and 14 exhibited potential inhibitory activity against PC-3 cells, while compounds 5–7, 14, and 16–17 displayed cytotoxic potency against Caco-2 cells. A preliminary structure-activity relationship was also discussed.

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 Δ

Five pairs of new 2-oxoindole alkaloids, (±)-peganumalines A-E (1-5), and a new indole alkaloid, peganumaline F (6), along with two known analogues, were isolated from the seeds of Peganum harmala. Their structures and absolute configurations were elucidated through spectroscopic analyses and quantum chemistry calculations. Notably, (±)-peganumalines A (1) represent a pair of rare 2-oxoindole dimeric alkaloid enantiomer with the hitherto unknown carbon skeleton. All isolates were tested for antiproliferative and antibacterial activities.

Three new diterpenoids, ebractenoids O ~ Q (1–3), and a new phenolic glucoside, γ-pyrone-3-O-β- d -(6-galloyl)-glucopyranoside (4), together with 6 known compounds, were isolated from the 95% ethanol extract of the roots of Euphorbia ebracteolata, and their structures were elucidated on the basis of spectroscopic data. The absolute configurations of 1–3 were determined by electronic circular dichroism (ECD) calculations. The inhibitory effects of all the isolates with exception of compounds 8 and 10 on the NO production in lipopolysaccharide (LPS)-induced macrophages were evaluated. All of them exhibited significant inhibitory activity.

Natural derived enmein-type diterpenoids exert cytotoxicity against a wide range of human cancer cells. Yet their medicinal applications are hindered by insufficient potency for chemotherapy. Hence, a series of novel enmein-type diterpenoid hybrids coupled with nitrogen mustards were designed and synthesized to increase antitumor efficacy while reducing systemic toxicity. Most conjugates exhibited stronger antiproliferative activities than parent diterpenoids and nitrogen mustards, especially for multidrug-resistant tumor cell line Bel-7402/5-FU. Among them, compound E2 showed the most potent inhibitory activities in human leukemia HL-60 cells, human prostate cancer PC-3 cells, human liver cancer Bel-7402 cells and drug-resistant human liver cancer Bel-7402/5-FU cells with IC50 values of 7.83 μM, 3.97 μM, 0.77 μM and 2.07 μM, respectively. Additionally, high selectivity with selectivity index over 130 was also observed from cytotoxic evaluation between L-02 human normal liver cells and Bel-7402 malignant liver cells. Further studies on mechanism of action indicated that E2 induced both apoptosis and G1 phase cell cycle arrest in Bel-7402 hepatoma cells. Moreover, the dysfunction in mitochondrial pathway was also involved in E2 initiated apoptotic activation, which entailed the loss of mitochondrial membrane potential followed by upregulating the bax/bcl-2 ratio and increasing the expression of cytochrome c, p53, caspase-3 and -9. Overall, E2 has the potential to emerge as a promising drug candidate for cancer therapy.

Protein tyrosine phosphatase 1B (PTP1B) is an attractive molecular target for anti-diabetes, anti-obesity, and anti-cancer drug development. From the seeds of Silybum marianum, nine flavonolignans, namely, silybins A, B (1, 2), isosilybins A, B (3, 4), silychristins A, B (5, 6), isosilychristin A (7), dehydrosilychristin A (8), and silydianin (11) were identified as a novel class of natural PTP1B inhibitors (IC50 1.3 7–23.87 µM). Analysis of structure–activity relationship suggested that the absolute configurations at C-7" and C-8" greatly affected the PTP1B inhibitory activity. Compounds 1–5 were demonstrated to be non-competitive inhibitors of PTP1B based on kinetic analyses. Molecular docking simulations resulted that 1–5 docked into the allosteric site, including α3, α6, and α7 helix of PTP1B. At a concentration inhibiting PTP1B completely, compounds 1–5 moderately inhibited VHR and SHP-2, and weakly inhibited TCPTP and SHP-1. These results suggested the potentiality of these PTP1B inhibitors as lead compounds for further drug developments., Graphical Abstract

Two new polyacylated germacrane sesquiterpenoids, named as salvianols A (1) and B (2), were isolated from the aerial parts of Salvia chinensis. Their structures were established by extensive analysis of HR-ESI-MS and NMR spectra. The polyacylated germacrane sesquiterpenoids are rare in natural products.

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.

A series of novel nitrogen mustard-evodiamine hybrids were synthesized and evaluated for their antitproliferative properties. The antiproliferative activities of 10a-d, 11a-d, and 12a-d against four different kinds of human cancer cell lines (PC-3, HepG2, THP-1 and HL-60) and human normal peripheral blood mononuclear cells (PBMC) were determined. The results showed that all the target hybrid compounds exhibited antiproliferative activities against tested human tumor cell lines to some extent and no antiproliferative activities (>200 μM) against human normal PBMC cells. The antiproliferative selectivity between tumorous and normal cells was very useful for further antitumor drug development. Among the target compounds, 12c showed the strongest cytotoxicity against two tumor cell lines (THP-1 and HL-60) with IC50 values of 4.05 μM and 0.50 μM, respectively, and selected for further mechanism study in HL-60 cells. The results showed that 12c could induce HL-60 cells apoptosis and arrest at G2 phase at low sub-micromolar concentrations via mitochondria-related pathways.

In the present study, the hypoglycemic effect of silychristin A on streptozotocin (STZ)-induced type 1 diabetes in rats was evaluated and the underlying pharmacological mechanism was further elucidated in vitro. Silychristin A significantly lowered the glucose level, increased insulin secretion, and improved the structure of β cells in STZ-induced rats. Accordantly, reactive oxygen species (ROS) production induced by STZ or high concentration of glucose (HG) was effectively suppressed by silychristin A in pancreatic INS-1 β cells evaluated by flow cytometry. Western blot analysis demonstrated that silychristin A markedly suppressed STZ or HG induced cell apoptosis. In addition, in vitro inhibitory effect of silychristin A on α-glucosidase and molecular docking analysis revealed that silychristin A could reduce the digestion rate of carbohydrates. These findings indicate that silychristin A may be useful as a potential functional food ingredient against oxidative stress-mediated destruction of pancreatic islet β cells and inhibition of α-glucosidase activity.

Vitex negundo L. var. heterophylla (Franch.) Rehd. is widely accepted as a functional and medicinal food in China because of the presence of bioactive components which improve the physical condition. In the present study, the bioactive constituents, antioxidant, α -glucosidase and DPP-IV inhibitory activities of V. negundo var. heterophylla were investigated. Two new coumarin glycosides, vitexnegheteroins I-J ( 1 – 2 ), and two new iridoid glycosides, vitexnegheteroins K-L ( 3 – 4 ), were isolated from the leaves and seeds of V. negundo var. heterophylla , together with twenty known compounds. Seven compounds presented stronger antioxidant activities than l -ascorbic acid in both DPPH and ABTS assays. Among them, isoorientin-6″- O -caffeate ( 22 ) also exhibited more potent α -glucosidase inhibitory activity than acarbose with an IC 50 value of 0.24 ± 0.02 μM. These findings further revealed the bioactive components of this edible aromatic plant and disclosed the potency of it to be developed as new antioxidant and α -glucosidase inhibitory agents.

A new biflavonoid, paucinervin K (1) and a new triterpene, 23-hydroxy-friedelin (2), together with eleven known compounds 3-13 were isolated from the leaves of Garcinia paucinervis. Their structures, including stereochemistry, were determined by spectroscopic analysis of NMR, MS, IR and ECD calculation and the octant rule. Some of the isolated compounds were tested for antiproliferative, α-glucosidase inhibitory and antioxidant activities in vitro. Compounds 1, 3, 4, 5 and 9 showed moderate preferential antioxidant and hypoglycemic activities. Compounds 3–6 and 9 exhibited potent growth inhibition against HepG-2 and PC-3 cell lines with IC50 values ranging from 1.02−10.05 μM.

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.

A novel α-pyrone substituted spiciferone, lecanicillolide (1), was isolated along with structurally related known compounds 2–4 from the fungus Lecanicillium sp. PR-M-3. The structure of lecanicillolide was elucidated by UV, IR, HRESIMS, and NMR spectral data, ECD analysis and confirmed by single-crystal X-ray diffraction. A plausible biosynthetic pathway for lecanicillolide was also proposed.

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 β-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,β-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.

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.

A new epipolythiodioxopiperazine (ETP), asperterzine ( 1 ), along with two known analogs, bisdethiobis(methylthio)-acetylaranotin ( 2 ) and bisdethiobis(methylthio)-acetylapoaranotin ( 3 ), was isolated from the plant endophytic fungus Aspergillus terreus PR-P-2. The structure elucidation of 1 was accomplished by a combination of spectral methods and electronic circular dichroism (ECD) spectrum. Asperterzine ( 1 ) was a symmetric aromatized ETP found as a natural product for the first time. Compounds 2 and 3 showed strong cytotoxicity against HL-60 cell line. The putative biosynthetic pathway of 1 was also detailed in the text.

Hydrogen sulfide (H2S) has been recognized as the third endogenous signaling gasotransmitter following nitric oxide (NO) and carbon monoxide (CO), and exhibits antiproliferative activity against several cancer cells. In order to stably and controllably release H2S, H2S donating compound (ADT-OH) was used in the present study and 18H2S releasing natural ent-kaurane diterpenoid oridonin derivatives were designed and synthesized. Most derivatives showed more potent antiproliferative activities than oridonin against HepG2 and K562 cell lines, while they were lack of sensitivity to HCT-116 and B16 cells. In particular, 12b showed the most potent antiproliferative activities against HepG2, HCT-116 and K562 cells with IC50 values of 2.57, 5.81 and 0.95 μM, respectively. Through cell cycle analysis, 12b caused cell cycle arrest at S phase in K562 cells and G1 phase in HepG2 cells. In Hoechst 33258 staining assay, cell shrinkage and fragmentation of cell nuclei indicated apoptotic morphological changes. Considering the decline of mitochondrial membrane potential and changes in the levels of apoptosis-related proteins, 12b was shown to induce apoptosis through extrinsic and intrinsic apoptosis pathways.

ObjectivesThe aim of this study was to investigate the molecular mechanisms of the efficacy of lignin compound dehydrodiconiferyl alcohol (DHCA) isolated from Silybum marianum (L.) Gaertn in improving wound healing. These findings preliminarily brought to light the promising therapeutic potential of DHCA in skin wound healing.MethodsFirst, the effect of DHCA on healing in vivo was studied using a full-thickness scalp wound model of mice by topical administration. Histopathological examinations were then conducted by haematoxylin and eosin (H&E), Masson’s trichrome staining and the immunofluorescence assay. Second, we further examined the anti-inflammatory mechanism of DHCA in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages by immunofluorescence assay and Western blot analysis.Key findingsDHCA could promote scalp wound healing in mice by enhancing epithelial cell proliferation and collagen formation and reducing inflammatory cells infiltration. Moreover, the NF-κB nuclear translocation was suppressed remarkably by DHCA administration in connective tissue of healing area. DHCA was also shown to inhibit production of nitric oxide (NO) and interleukin (IL)-1β with downregulated inducible nitric oxide synthase (iNOS) expression in LPS-induced RAW 246.7 cells. More importantly, DHCA administration upregulated p-IκBα expression and induced nuclear translocation of NF-κB without affecting its expression.ConclusionsOur study indicated that DHCA exerted anti-inflammatory activity through inactivation of NF-κB pathways in macrophages and subsequently improved wound healing.

Macleayine (1), a new natural occurring alkaloid with a unique spiro [furanone-piperidinedione] framework, was isolated from the aerial parts of Macleaya cordata. Its unusual structure was established by extensive spectroscopic analyses, computer-assisted structure elucidation software (ACD/Structure Elucidator), quantum chemistry calculations and ECD calculation. The result of virtual molecular docking predicted the compound can enhance the effects of insulin, and may be used to treat type II diabetes.

Herein, we reported the cytotoxicity, NO-releasing property, and apoptosis induced ability of two series of novel nitric oxide-releasing spirolactone-type diterpenoid derivatives (10a–f and 15a–f). All the title compounds were more potent than oridonin (7) and parent compound (9 or 14) against human tumor Bel-7402, K562, MGC-803 and CaEs-17 cells. SARs were concluded based on above data. Compound 15d exhibited the strongest antiproliferative activity with the IC50 of 0.86, 1.74, 1.16 and 3.75 μM, respectively, and could produce high level (above 25 μM) of NO at the time point of 60 min. Further mechanism evaluation showed that 15d could induce S phase cell cycle arrest and apoptosis at low micromolar concentrations in Bel-7402 cells via mitochondria-related pathways. It was expected that the remarkable biological profile of the synthetic NO-releasing spirolactone-type diterpenoid analogs make them possible as promising candidates for the development of anticancer agents.

Four new polyketide-derived polyesters, including three linear ones ascotrichesters A–C (1–3) and one macrocyclic ascotrichalactone A (4), and the known biosynthetic building blocks (−)-orthosporin (7) and (−)-6-hydroxymellein (8), were isolated from the still culture product of the fungus Ascotricha sp. ZJ-M-5 in Czapek Dox broth without Mg2+, along with a new hexaketide orthosporinin (5) and its visible light-catalyzed [2+2] dimerized derivative diorthosporinin (6). HPLC monitoring of the stability of 4 in H2O disclosed the fact that macrocyclic lactone 4, with a unreported motif for polyesters, 2,4-dihydroxy-6-(4-hydroxy-2-oxopentyl)benzoic acid, is the natural precursor which undergoes hydrolysis followed by intramolecular lactonization at pH 7 or 8 to yield the linear polyester 3 and parallel reactions to afford 5. This result demonstrated that the previously proposed biosynthetic pathway for polyesters from linear to cyclic should be reversed. Additionally, the growth inhibitory effects of 1–8 against two human leukemia cancer cell lines and the antibacterial activities of compounds 3 and 4 were assessed.

Four new coumarins, namely (−)-12-methoxyinophyllum A, (+)-12-methoxyinophyllum H-1, (-)-12-methoxyinophyllum H-2, and inophyllum J, along with two known compounds, 12-ethoxyinophyllum D and isoinophynone were isolated from the leaves of Calophyllum inophyllum . Their structures were elucidated by spectroscopic analyses, and complete assignments of 1 H and 13 C NMR spectroscopic data were achieved by 1D and 2D NMR experiments.

Lecanicillones A–C (1–3), three unusual dimeric spiciferones with acyclobutane ring via a [2 + 2] cycloaddition, were isolated from an entomopathogenic fungus Lecanicillium sp. PR-M-3. The structures of 1–3 were elucidated on the basis of spectral data, single-crystal X-ray diffraction, and ECD analysis. Compounds 1 and 3 showed moderate cytotoxicity against the HL-60 cell line.

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.

Three pairs of new enantiomeric natural alkaloids (±)-macleayins C–E (1–3), together with five pairs of known racemic alkaloids (4–8), were isolated from the aerial parts of Macleaya cordata. Compounds 1–5 were separated successfully by chiral-phase HPLC to yield optically pure isomers. However, chiral resolution of compounds 6–8 existing as racemers in the plant was unsuccessful. It is noteworthy that, macleayin C represents a novel type of hybrid composed of a dihydrobenzophenanthridine alkaloid and a phenylpropanoid. The structures including the absolute configurations of (±)-1–5 were established by detailed spectroscopic analyses and electronic circular dichroism calculations. All the isolates were evaluated for in vitro anti-tumor and antibacterial activities, and compounds (±)-4–5 exhibited potent cytotoxicity against HL-60 cell lines with IC50 values less than 3.0 μM, and compounds (±)-1–3 showed moderate cytotoxic activity. Only compound 7 revealed inhibitory activities against Staphylococcus aureus, Bacillus subtilis, and Candida albicans with MIC values of 33.07, 8.27, and 8.27 μg mL−1, respectively.

Four new phenolic compounds, vitexnegheteroins A–D (1–4), were isolated from the seeds of Vitex negundo var. heterophylla, together with eight known compounds. Their structures were established on the basis of extensive 1D and 2D NMR experiments, as well as their mass spectroscopic data. The absolute configuration of compound 4 was determined by comparing its experimental CD spectrum with that calculated by the time-dependent density functional theory (TDDFT) method. The antioxidant and anti-inflammatory activities of these phenolics were also evaluated. Most of the compounds showed strong ABTS radical scavenging activities and all the tested isolates exhibited inhibitory effects on lipopolysaccharide-induced NO production in murine microglial BV-2 cells. The bioactive studies supported the traditional use of this edible aromatic plant and disclosed the potency of it to be developed as new antioxidant and anti-inflammatory functional food.

Cephafortunoids A–D (1–4), four new compounds, together with ten known ones (5–14), were isolated from the branches and leaves of Cephalotaxus fortunei var. alpina. 1 and 2 represent the first examples of Cephalotaxus troponoid diterpenoids featured an intact C20 skeleton with CH3-17 migrating to C-15 and C-13 respectively. 3 and 4 are novel cephalotane-type diterpenoids with an epoxy ring between C-12 and C-13. The structures of isolated compounds were established by extensive spectroscopic methods, electronic circular dichroism (ECD) calculations, and comparison with reported data. In in vitro bioassays, all isolated compounds were evaluated for their cytotoxic activities against human promyelocytic leukemia cells (HL-60), human acute monocytic leukemia cells (THP-1), human breast cancer cells (MDA-MB-231), and human prostate cancer cells (PC-3). 5–9 exhibited prominent cytotoxicity against HL-60 and THP-1 with GI50 values of 0.27–5.48 and 0.48–7.54 μM, respectively. 5–8 showed evident cytotoxicity against MDA-MB-231 and PC-3 with IC50 values of 1.96–10.66 and 2.72–13.99 μM, severally. 6 with an IC50 value of 2.72 ± 0.35 μM displayed stronger cytotoxicity against PC-3 than the positive control etoposide. The structure-activity relationship of these compounds and plausible biogenetic pathways for 1–4 were discussed.