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The 2015 Nobel Prize in Physiology or Medicine, shared by Professor Youyou Tu, focused worldwide attention on artemisinin, a natural product antimalarial drug inspired by traditional Chinese medicine (TCM). This is the first Nobel Prize in natural sciences presented to a Chinese scientist for her impactful research work in China in collaboration with other Chinese scientists. We are delighted to provide the background and implications of the discovery of artemisinin, along with our personal viewpoints toward the affordability of modern medicines from natural products. [ABSTRACT FROM AUTHOR]

The correction notice for the article "Circular RNA-encoded oncogenic PIAS1 variant blocks immunogenic ferroptosis by modulating the balance between SUMOylation and phosphorylation of STAT1" in Molecular Cancer addresses inaccuracies in Figures 2 and 3. The errors involve incorrect loading controls and a recommendation to change the vertical title in Figure 3-a for improved accuracy. The correction was made by Xin Zang, Xiao‑Yu He, Cheng‑Mei Xiao, Qing Lin, Meng‑Yue Wang, Cheng‑Yan Liu, Ling‑Yi Kong, Zhong Chen, and Yuan‑Zheng Xia. [Extracted from the article]

Two new resin glycosides, batataosides I (1) and II (2), and five known compounds, friedelin (3), scopoletin (4), octadecyl caffeate (5), β-sistosterol (6) and daucosterol (7), were isolated from the roots of Ipomoea batatas. Their structures have been determined based on the chemical and spectral data. Batataosides I and II have novel structures because the core simonic acid B was esterised with cinnamic acid for the first time, and three different substituent esterification groups in one resin glycoside is scarce. The absolute configuration of the aglycone was elucidated to be S by Mosher's method. [ABSTRACT FROM AUTHOR]

Abstract: One new and three known triterpenes were isolated from roots of Angelica cartilagino-marginata var. foliata Yuan et Shan. The structures of the new compounds were determined by modern spectroscopic techniques, including 2D NMR experiments. These triterpenes are important characters in chemosystematics of Umbelliferae. [Copyright &y& Elsevier]

Two new compounds, 2α-( p -hydroxycinnamoyl) cineole ( 2 ) and ( E )-15-nor-16-oxo-8(17),12-labdadiene ( 4 ), along with three known compounds, trans -cinnamyl methyl ester ( 1 ), 4(15)-cadinene-6,10-diol ( 3 ) and isorhamnetin-3- O -β- d -galactosyl-(6→1)-α- l -rhamnoside ( 5 ), have been isolated from Alpinia tonkinensis Gangep. Their structures have been elucidated by spectral analysis. [ABSTRACT FROM AUTHOR]

A new angular dihydropyrancoumarin named wulongensin A, along with five known coumarins, (-)-anomalin, umbelliferone, (-)-smyrinol, 3′( S ),4′( S )-disenecioyloxy-3′,4′-dihydroseselin, (+)- trans -khellactone, was isolated from the root of Peucedanum wulongense . The structure of wulongensin A was established as 3′( R )-angeloyloxy-4′( R )-isovaleryloxy-3′,4′-dihydroseselin by spectroscopic methods and the absolute configurations were deduced by chemical correlations with known compounds. [ABSTRACT FROM AUTHOR]

Background: The clinical response rate to immune checkpoint blockade (ICB) therapy in melanoma remains low, despite its widespread use. Circular non-coding RNAs (circRNAs) are known to play a crucial role in cancer progression and may be a key factor limiting the effectiveness of ICB treatment. Methods: The circRNAs that were downregulated after coadministration compared with single administration of PD-1 inhibitor administration were identified through RNA-seq and Ribo-seq, and thus the circPIAS1 (mmu_circ_0015773 in mouse, has_circ_0008378 in human) with high protein coding potential was revealed. Fluorescence in situ hybridization (FISH) assays were conducted to determine the localization of circPIAS1 in human and mouse melanoma cells, as well as its presence in tumor and adjacent tissues of patients. Validation through dual-luciferase reporter assay and LC–MS/MS confirmed the ability of circPIAS1 to encode a novel 108 amino acid polypeptide (circPIAS1-108aa). Specific antisense oligonucleotides (ASOs) targeting the junction site of circPIAS1 were developed to reduce its intracellular levels. Proliferation changes in melanoma cells were assessed using CCK8, EdU, and colony formation assays. The impact of circPIAS1-108aa on the ferroptosis process of melanoma cells was studied through GSH, MDA, and C11-BODIPY staining assays. Western Blot, Immunoprecipitation (IP), and Immunoprecipitation-Mass Spectrometry (IP-MS) techniques were employed to investigate the impact of circPIAS1-108aa on the P-STAT1/SLC7A11/GPX4 signaling pathway, as well as its influence on the balance between STAT1 SUMOylation and phosphorylation. Additionally, a melanoma subcutaneous transplanted tumor mouse model was utilized to examine the combined effect of reducing circPIAS1 levels alongside PD-1 inhibitor. Results: Compared with the group treated with PD-1 inhibitor alone, circPIAS1 was significantly down-regulated in the coadministration group and demonstrated higher protein coding potential. CircPIAS1, primarily localized in the nucleus, was notably upregulated in tumor tissues compared to adjacent tissues, where it plays a crucial role in promoting cancer cell proliferation. This circRNA can encode a unique polypeptide consisting of 108 amino acids, through which it exerts its cancer-promoting function and impedes the effectiveness of ICB therapy. Mechanistically, circPIAS1-108aa hinders STAT1 phosphorylation by recruiting SUMO E3 ligase Ranbp2 to enhance STAT1 SUMOylation, thereby reactivating the transduction of the SLC7A11/GPX4 signaling pathway and restricting the immunogenic ferroptosis induced by IFNγ. Furthermore, the combination of ASO-circPIAS1 with PD-1 inhibitor effectively inhibits melanoma growth and significantly enhances the efficacy of immune drugs in vivo. Conclusions: Our study uncovers a novel mechanism regarding immune evasion in melanoma driven by a unique 108aa peptide encoded by circPIAS1 in melanoma that dramatically hinders immunogenic ferroptosis triggered by ICB therapy via modulating the balance between SUMOylation and phosphorylation of STAT1. This work reveals circPIAS1-108aa as a critical factor limiting the immunotherapeutic effects in melanoma and propose a promising strategy for improving ICB treatment outcomes. [ABSTRACT FROM AUTHOR]

The phase-field-crystal (PFC) method is used to investigate migration of grain boundary dislocation and dynamic of strain-driven nucleation and growth of deformed grain in two dimensions. The simulated results show that the deformed grain nucleates through forming a gap with higher strain energy between the two sub-grain boundaries (SGB) which is split from grain boundary (GB) under applied biaxial strain, and results in the formation of high-density ensembles of cooperative dislocation movement (CDM) that is capable of plastic flow localization (deformed band), which is related to the change of the crystal lattice orientation due to instability of the orientation. The deformed grain stores the strain energy through collective climbing of the dislocation, as well as changing the orientation of the original grain. The deformed grain growth (DGG) is such that the higher strain energy region extends to the lower strain energy region, and its area increase is proportional to the time square. The rule of the time square of the DGG can also be deduced by establishing the dynamic equation of the dislocation of the strain-driven SGB. The copper metal is taken as an example of the calculation, and the obtained result is a good agreement with that of the experiment. [ABSTRACT FROM AUTHOR]

Four new nortriterpenoid alkaloids, namely buxrugulines E–H (1–4), along with five known ones (5–9), were isolated from the twigs and leaves of Buxus rugulosa. Their structures were identified based on extensive NMR data and MS spectroscopic analyses. Our bioassays revealed that compounds 5, 6 and 8 exhibited potent cytotoxicity in vitro against MCF-7 cell lines, with IC50 values ranging from 6.70 to 11.00 μM, respectively. [ABSTRACT FROM AUTHOR]

Two novel limonoids named spirotrichilins A (I) and B (II) are obtained from the fruits of trichilia connaroides. [ABSTRACT FROM AUTHOR]

Involudispirones A (I), and B (II), a pair of cytotoxic sesterpene stereoisomers, containing an unusual dioxadispiro[5.2.5.2]hexadecane ring system as their most intriguing structures, are isolated from the rhizomes of S. [ABSTRACT FROM AUTHOR]

Background and Purpose Experimental Approach Key Results Conclusions and Implications Chaperone‐mediated autophagy (CMA) is a selective type of autophagy targeting protein degradation and maintains high activity in many malignancies. Inhibition of the combination of HSC70 and LAMP2A can potently block CMA. At present, knockdown of LAMP2A remains the most specific method for inhibiting CMA and chemical inhibitors against CMA have not yet been discovered.Levels of CMA in non‐small cell lung cancer (NSCLC) tissue samples were confirmed by tyramide signal amplification dual immunofluorescence assay. High‐content screening was performed based on CMA activity, to identify potential inhibitors of CMA. Inhibitor targets were determined by drug affinity responsive target stability‐mass spectrum and confirmed by protein mass spectrometry. CMA was inhibited and activated to elucidate the molecular mechanism of the CMA inhibitor.Suppression of interactions between HSC70 and LAMP2A blocked CMA in NSCLC, restraining tumour growth. Polyphyllin D (PPD) was identified as a targeted CMA small‐molecule inhibitor through disrupting HSC70–LAMP2A interactions. The binding sites for PPD were E129 and T278 at the nucleotide‐binding domain of HSC70 and C‐terminal of LAMP2A, respectively. PPD accelerated unfolded protein generation to induce reactive oxygen species (ROS) accumulation by inhibiting HSC70–LAMP2A–eIF2α signalling axis. Also, PPD prevented regulatory compensation of macroautophagy induced by CMA inhibition via blocking the STX17–SNAP29–VAMP8 signalling axis.PPD is a targeted CMA inhibitor that blocked both HSC70–LAMP2A interactions and LAMP2A homo‐multimerization. CMA suppression without increasing the regulatory compensation from macroautophagy is a good strategy for NSCLC therapy. [ABSTRACT FROM AUTHOR]

The title compound, C24H16Cl2O4, has non-crystallographic twofold rotational symmetry and the double bonds of the cinnamoyl groups adopt E configurations. Mol­ecules are linked via C—H⋯O inter­actions, forming zigzag chains along the c axis. [ABSTRACT FROM AUTHOR]

Eight new compounds, including four rare B- seco -29-nor-limonoids, toonaciliatones A-D ( 1 – 4 ), and four normal B- seco -limonoids, toonaciliatones E-H ( 5 – 8 ), together with six known compounds ( 9–14 ), were isolated from the stem barks of Toona ciliata var. yunnanensis . Toonaciliatones A and B ( 1 – 2 ) are the first examples of B- seco -29-nor-limonoids without the common five-membered 4, 7-lactone. Their structures were elucidated by extensive spectroscopic analysis including UV, IR, NMR and HRMS, and the absolute configurations of isolates with α, β-unsaturated ketone moiety ( 1 , 5 – 7 ) were determined by CD exciton chirality method and electronic circular dichroism (ECD) calculation. Compounds 3 and 11 exhibited modest cytotoxicities against HL-60 and HepG2 cells. [ABSTRACT FROM AUTHOR]

Five new limonoids, aphagranols D-H ( 1- 5, resp.), were isolated from the EtOH extract of the fruits of Aphanamixis grandifolia by chromatographic methods. Their structures were established on the basis of extensive spectroscopic analyses. The absolute configuration of 1 was determined by comparison the experimental and calculated electronic circular dichroism (ECD) spectra. All of the isolates were evaluated for insecticidal activities. [ABSTRACT FROM AUTHOR]

Highlights: [•] Four new cholestane-type and two new ergostane-type steroids were isolated from leaves of Dysoxylum binecteriferum. [•] The absolute configurations were established by Mo2(OAc)4-induced electronic circular dichroism (ECD) data. [•] Three cholestane-type steroids 2, 3, 4 were found to show moderate cytotoxic activities. [Copyright &y& Elsevier]

Two new monoterpenes, (7S)-p-cymene-2,7,8-triol (1) and (3R,4R,6S)-p-menth-1-ene-3,6,10-triol (2), were isolated from the fruits of Amomum kravanh. Their structures were established by spectroscopic data. The absolute configuration of the 7,8-diol moiety in 1 was assigned by CD data after addition of Mo2(OAc)4 in dimethyl sulfoxide (DMSO) solution. Compounds 1 and 2 exhibited weak activity of anti-platelet aggregation in vitro. [ABSTRACT FROM AUTHOR]

[Display omitted] • Piperine derivatives were designed and synthesized as novel h DHODH inhibitors. • H19 showed the strongest cytotoxic and h DHODH inhibitory activities among all the synthesized compounds. • H19 could effectively inhibit the proliferation of NCI-H226 cells by inducing ferroptosis. Inhibition of human dihydroorotate dehydrogenase (h DHODH) represents a promising strategy for suppressing the proliferation of cancer cells. To identify novel and potent h DHODH inhibitors, a total of 28 piperine derivatives were designed and synthesized. Their cytotoxicities against three human cancer cell lines (NCI-H226, HCT-116, and MDA-MB-231) and h DHODH inhibitory activities were also evaluated. Among them, compound H19 , exhibited the strongest inhibitory activities (NCI-H226 IC 50 = 0.95 µM, h DHODH IC 50 = 0.21 µM). Further pharmacological investigations revealed that H19 exerted anticancer effects by inducing ferroptosis in NCI-H226 cells, with its cytotoxicity being reversed by ferroptosis inhibitors. This was supported by the intracellular growth or decline of ferroptosis markers, including lipid peroxidation, Fe2+, GSH, and 4-HNE. Overall, H19 emerges as a promising h DHODH inhibitor with potential anticancer properties warranting development. [ABSTRACT FROM AUTHOR]

Abstract: A series of imine resveratrol derivatives (1–20) have been designed, synthesized, and evaluated as multi-targeted compounds for the treatment of Alzheimer's disease (AD). In vitro studies show that most of the molecules exhibit a significant ability to inhibit self-induced and Cu2+-induced β-amyloid (Aβ 1–42) aggregation, and to function as potential antioxidants and biometal chelators. In particular, compound 9 is a potential lead compound for AD treatment (for compound 9, IC50 = 14.1 μM for the antioxidant activity using DPPH free radical method; 64.6% at 20 μM for self-induced Aβ aggregation). Moreover, it is capable of decreasing reactive oxygen species (ROS) induced by Cu-Aβ and shows good neuroprotective effects in human SH-SY5Y neuroblastoma cells. Taken together, these results suggest that 9 might be a promising lead compound for AD treatment. [Copyright &y& Elsevier]

Two new Lycopodium alkaloids, (+)-cermizine D N-oxide ( 1) and (8 β)-8-(acetyloxy)obscurumine A ( 2), along with five known compounds, were isolated from the crude alkaloid portion of Lycopodium obscurum. Their structures were elucidated on the basis of spectroscopic data and chemical correlation. All of these alkaloids were tested in an assay for acetylcholine esterase (AChE) inhibitory activity. [ABSTRACT FROM AUTHOR]

Chemical investigation on the crude alkaloid portion of Lycopodium obscurum led to isolation of three new fawcettimine-type Lycopodium alkaloids, lycobscurines A–C (1–3), together with three known compounds. Their structures were determined by spectroscopic methods including HR-ESI-MS and NMR techniques. All compounds were tested in an assay for acetylcholinesterase inhibitory activity. [ABSTRACT FROM AUTHOR]

Abstract: A novel domino reaction catalyzed by an organic molecule based on α,β-unsaturated aromatic aldehydes and methylethylketones has been developed. The progress allows one-pot and efficient synthesis of polysubstituted 4-oxocyclohexanecarbaldehyde derivatives via pyrrolidine mediated under mild conditions. The reaction consists of three consecutive reactions: an aldol condensation reaction and a tandem inter-Michael–intra-Michael addition reaction. [Copyright &y& Elsevier]

Abstract: From the flowers of Chrysanthemum indicum, three new germacrane-type sesquiterpene stereoisomers (1β,3α,5β-trihydroxyl-7-isopropenyl-germacren-4(15), 10(14)-diene (1), 1β,3β,5α-trihydroxyl-7-isopropenyl-germacren-4(15), 10(14)-diene (2), 1β,3β,5β-trihydroxyl-7-isopropenyl-germacren-4(15), 10(14)-diene (3)) were isolated, whose structures were elucidated on the basis of extensive spectroscopic analysis. The absolute configuration of compound 1 was determined by a single crystal X-ray diffraction study using a mirror Cu Kα radiation. [Copyright &y& Elsevier]

Two new tocopherol polymers, chroman-type dimer named ferotocodimer A (1) and spiro-type trimer named ferotocotrimer E (2), were isolated from the seeds of Euryale ferox. Their structures were elucidated on the basis of spectroscopic methods including HR-ESI-MS and 1D and 2D NMR. The absolute configurations of 1 and 2 were determined by CD and ROESY experiments. [ABSTRACT FROM PUBLISHER]

Two rare new chlorophenyl glycosides, 2,4,6-trichlorol-3-methyl-5-methoxy-phenol 1-O-β-d-glucopyranosyl-(1 → 6)-β-d-glucopyranoside (1) and 4-chlorol-5-hydroxyl-3-methyl-phenol 1-O-α-l-rhamnopyranosyl-(1 → 6)-β-d-glucopyranoside (2), along with three known compounds (3–5) were isolated from the bulbs of Lilium brownii var. viridulum. The structures of the new compounds were elucidated on the basis of spectroscopic and chemical methods. All the compounds exhibited weak inhibition of NO production in LPS-stimulated RAW 264.7 cells. [ABSTRACT FROM PUBLISHER]

Abstract: Nine new triterpenoid saponins (1–9) have been isolated from the roots of Gypsophila perfoliata Linn. Their structures were established on the basis of extensive NMR (1H, 13C, HSQC and HMBC) and ESIMS studies. [Copyright &y& Elsevier]

Three new sulfated triterpenoids (1-3), along with one known compound (4), were isolated from the roots of Gypsophila pacifica Kom. The structures of the new compounds were established as 3β-O-sulfate gypsogenin 28-O-β-d-glucopyranosyl ester (1), 3β-O-sulfate gypsogenin (2), and 3β-O-sulfate quillaic acid (3) on the basis of 1D, 2D NMR, and HR-ESI-MS methods. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: Huang-Lian-Jie-Du decoction (HLJDD) (Oren-gedoku-to in Japanese) as a famous traditional Chinese recipe is composed of Rhizoma coptidis, Radix scutellariae, Cortex phellodendri and Fructus gardeniae. It has been used to treat inflammation for nearly two thousand years. Aim of the study: To explore the material base for the anti-inflammatory activity of formula HLJDD, its extract was fractionated on D101 macroporous resin to afford two fractions, HLJDD-1 and HLJDD-2. The whole formula, HLJDD-1 and HLJDD-2, and four typical component compounds were then evaluated for their effects on inflammation-related parameters using lipopolysaccharide (LPS)-induced RAW264.7 cells as a model system. Materials and methods: The effect of HLJDD on carrageenan-induced mice paw edema was first evaluated. A series of inflammation-related parameters including malondialdehyde (MDA), nitric oxide (NO), superoxide dismutase (SOD), prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-10 (IL-10) were then measured in LPS-induced RAW264.7 cells treated with HLJDD, its two fractions, and four typical component compounds (geniposide, baicalin, berberine and baicalein). Results: With the help of principal component analysis (PCA) technique, the data obtained revealed that the two fractions and the major group of compounds in HLJDD (iridoids, flavonoids and alkaloids) complement each other with particular emphasis to synergistically exert anti-inflammatory effects. Conclusions: This study demonstrated that HLJDD exhibited anti-inflammatory effect as a “whole”, which justified the combined use of the four component herbs forming the compound prescription and suggested quality control of HLJDD based on its three types of components. [Copyright &y& Elsevier]

Abstract: Danggui-Shaoyao-San (DSS), a traditional Chinese medicinal prescription, is clinically used for the treatment of vascular dementia (VD). This study compared the pharmacokinetics of paeoniflorin, the main active ingredients in Paeonia lactiflora Pall, in VD and normal rats administrated with DSS or pure paeoniflorin. The absorptions of paeoniflorin in both VD and normal group of rats were better when orally administrated with DSS than that with pure paeoniflorin, which justified the combined use as formula DSS. Moreover, a better absorption of paeoniflorin in rats of the VD than in normal group was observed, which is helpful for the treatment of VD. [Copyright &y& Elsevier]

Two new triterpenoid saponins (1 and 2) were isolated from the dried aerial parts of Dianthus superbus L. (Caryophyllaceae). Their structures were elucidated on the basis of spectral data to be 3-O-β-D-glucopyranosyl olean-9(11),12-diene-23,28-dioic acid 28-O-β-D-glucopyranoside (1) and 3-O-β-D-glucopyranosyl olean-11,13(18)-diene-23,28-dioic acid 28-O-β-D-glucopyranoside (2). [ABSTRACT FROM AUTHOR]

Abstract: Six new triterpenoid saponins (1–6) have been isolated from the roots of Gypsophila pacifica Kom. Their structures were established on the basis of extensive NMR (1H, 13C, TOCSY, HSQC, and HMBC) and ESIMS studies. [Copyright &y& Elsevier]

Two new coumarin glycosides (1 and 2), along with six known compounds (3-8), were isolated from the roots of Euphorbia soongarica. The structures of two new compounds were elucidated as aesculetin-6-O-(6'-O-galloyl)-β-d-galactopyranoside (1) and fraxetin-8-O-(6'-O-galloyl)-β-d-galactopyranoside (2) by spectral methods and chemical evidences. [ABSTRACT FROM AUTHOR]

One new (Sarsasapogenin O) and seven known steroids were isolated from the roots of Asparagus officinalis L. Their structures were elucidated on the basis of spectroscopic analysis, including various 2D-NMR techniques, hydrolysis, and by comparison of spectral data of known compounds. These compounds together with nine steroids which were previously isolated from this plant, were tested for cytotoxic activity. Among them, eight compounds displayed significant cytotoxicities against human A2780, HO-8910, Eca-109, MGC-803, CNE, LTEP-a-2, KB and mouse L1210 tumor cells. [ABSTRACT FROM AUTHOR]

Abstract: Seven new triterpenoid saponins (1–7), have been isolated and elucidated from the roots of Gypsophila oldhamiana together with five known triterpenoid saponins (8–12). These saponins which could be classified into three series: 3-O-monoglucosides (1, 8, 9), 28-O-monoglucosides (2–4, 12) and 3, 28-O-bidesmosides (5–7, 10, 11), have been evaluated for their α-glucosidase inhibition activity. As a result, the preliminary structure–activity relationships were discussed based on the position of sugar linkage attached to the aglycone, and 28-O-monoglucosides 2–4 and 12 showed significant inhibitory activities on α-glucosidase. [Copyright &y& Elsevier]

A new compound, 3′( R )- O -β- d -glucopyranosyl-3′,4′-dihydroxanthyletin ( 1 ), and a known compound, prim-O-glucosylcimifugin ( 2 ), were isolated from the roots of Peucedanum dissolutum . The structure of 1 was elucidated by spectral evidence and chemical reaction. The NMR signals of carbons and protons of 2 were assigned for the first time by analysis of 1 H- 1 H COSY, HMQC and HMBC spectra. [ABSTRACT FROM AUTHOR]

Seven pairs of undescribed monoterpenoid polyprenylated acylphloroglucinol enantiomers [(±)-hypermonanones A-G (1 – 7)], together with three known analogues, were identified from the whole plant of Hypericum monanthemum Hook. The structures of these compounds were determined by analyses of their UV, HRESIMS, 1D/2D NMR spectroscopic data, and NMR calculations. The absolute configurations of these compounds were assigned by ECD calculations after chiral HPLC separation. Diverse monoterpene moieties were fused at C-3/C-4 of the dearomatized acylphloroglucinol core, which led to 3,4-dihydro-2 H -pyran-integrated angular or linear type 6/6/6 tricyclic skeletons in 1 – 7. Compounds (−)- 2 and (+)- 2 exhibited significant NO inhibitory activity against LPS induced RAW264.7 cells with the IC 50 values of 7.07 ± 1.02 μM and 11.39 ± 0.24 μM, respectively. [Display omitted] [ABSTRACT FROM AUTHOR]

• A natural xanthone was screened as a new antifungal agent targeting GAPDH. • The lead compound XP-W has a good safety profile. • XP-W exhibits a 50-fold selectivity for GAPDH from Candida versus human. • XP-W displays broad-spectrum anti- Candida and anti-biofilm activity. This study aimed to discover novel antifungals targeting Candida albicans glyceraldehyde-3-phosphate dehydrogenase (Ca GAPDH), have an insight into inhibitory mode, and provide evidence supporting Ca GAPDH as a target for new antifungals. Virtual screening was utilized to discover inhibitors of Ca GAPDH. The inhibitory effect on cellular GAPDH was evaluated by determining the levels of ATP, NAD, NADH, etc., as well as examining GAPDH mRNA and protein expression. The role of GAPDH inhibition in C. albicans was supported by drug affinity responsive target stability and overexpression experiments. The mechanism of Ca GAPDH inhibition was elucidated by Michaelis-Menten enzyme kinetics and site-specific mutagenesis based on docking. Chemical synthesis was used to produce an improved candidate. Different sources of GAPDH were used to evaluate inhibitory selectivity across species. In vitro and in vivo antifungal tests, along with anti-biofilm activity, were carried out to evaluate antifungal potential of GAPDH inhibitors. A natural xanthone was identified as the first competitive inhibitor of Ca GAPDH. It demonstrated in vitro anti- C. albicans potential but also caused hemolysis. XP-W, a synthetic side-chain-optimized xanthone, demonstrated a better safety profile, exhibiting a 50-fold selectivity for Ca GAPDH over human GAPDH. XP-W also exhibited potent anti-biofilm activity and displayed broad-spectrum anti- Candida activities in vitro and in vivo, including multi-azole-resistant C. albicans. These results demonstrate for the first time that Ca GAPDH is a valuable target for antifungal drug discovery, and XP-W provides a promising lead. XP-W, the first competitive and selective Ca GAPDH inhibitors, displayed broad-spectrum anti- Candida activities and a good safety profile. [Display omitted] [ABSTRACT FROM AUTHOR]

A new andirobin-type limonoid with modified furan ring, khaysenelide K (1), together with a known analogue (2), was isolated from the stem barks of Khaya senegalensis. The structure and absolute configuration of 1 were elucidated by a combination of 1D and 2D NMR, HRESIMS, and single-crystal X-ray diffraction using mirror Cu-Kα radiation. Compound 1 showed moderate NO inhibitory activity in LPS-activated RAW 264.7 macrophages with IC50 value of 27.74 ± 0.68 μM. [ABSTRACT FROM AUTHOR]

Non-alcoholic steatohepatitis (NASH) is the progressive stage of non-alcoholic fatty liver disease that may ultimately lead to cirrhosis and liver cancer, and there are few therapeutic options for its treatment. Physalin B (PB), a withanolide isolated from Physalis species (Solanaceae), exhibits a broad spectrum of biological activities, however, the potential role of PB in NASH has not been evaluated. The present study investigated the protective effects of PB against NASH and further elucidated the mechanisms of PB in hepatic autophagy and oxidative stress in vitro and in vivo. We conducted a series of experiments using methionine-choline deficient (MCD) diet induced NASH mice and cultured L02 cells. Serum markers of liver injury, morphology, and the histology of liver tissues were investigated. Western blot assays and quantitative real-time PCR were used to investigate the hepatoprotective effect of PB. PB significantly ameliorated hepatic injury, including hepatic index, transaminase activities, histology, and inflammation in MCD-induced mice. Moreover, PB markedly increased the expression of P62 and the ratio of LC3Ⅱ/Ⅰ in vitro and in vivo. Furthermore, PB promoted the interaction between endogenous KEAP1 and P62, reduced the interaction between KEAP1 and NRF2, activated the nuclear translocation of NRF2 and NRF2 target gene expression, and ultimately attenuated oxidative stress. In addition, knockdown of P62 blocked PB-mediated activation of NRF2 in L02 cells. These results clearly indicated that PB ameliorated NASH by stimulating autophagy and P62-KEAP1-NRF2 antioxidative signaling, suggesting that PB is expected to become a novel therapeutic drug for NASH. Image 1 • PB attenuated NASH progression. • PB upregulated the autophagy activity. • PB upregulated the expression and nuclear translocation of NRF2. • PB increased P62 expression and interfered with the interaction between KEAP1 and NRF2. [ABSTRACT FROM AUTHOR]

Taxodisones A and B, C30-terpenes with an unprecedented tetracyclo[12.4.0.0.2,709,14]octodecane core, were isolated from the seeds of Taxodium distichum. Their structures, including their configurations, were unambiguously determined. Their biomimetic synthesis suggests that they stem from diterpenes and monoterpenes, and not from squalene or oxidosqualene. In addition, their bioactivities were also evaluated. [ABSTRACT FROM AUTHOR]

Abstract: Elaborate study on the three-dimensional model of α1-adrenoceptor (α1-AR) antagonists led to the development of a series of new arylpiperazine derivatives bearing a flavone nucleus as α1-AR antagonists. The in vitro activities were evaluated and compounds 1, 4, 10, 13 and 15 showed activities close to the reference compound (Prazosin). [ABSTRACT FROM AUTHOR]

In this research, five new indolequinazoline alkaloids (1 – 5), along with six known indolequinazoline alkaloids (6 – 11) were obtained from the fruits of Tetradium ruticarpum. Their structures were elucidated through comprehensive spectroscopic data of 1D and 2D NMR, HRESIMS and ECD spectra. Additionally, all isolates were assayed for their SIRT1 inhibitory activities in vitro and compounds 2 , 7 , 10 and 11 exhibited activities with IC 50 values ranged from 43.16 to 118.35 μM. Eleven indolequinazoline alkaloids, including five undescribed compounds, were isolated from the fruits of Tetradium ruticarpum and their SIRT1 inhibitory activities were assessed. [Display omitted] [ABSTRACT FROM AUTHOR]

The involvement of CDC20 in promoting tumor growth in different types of human cancers and it disturbs the process of cell division and impedes tumor proliferation. In this work, a novel of Apcin derivatives targeting CDC20 were designed and synthesized to evaluate for their biological activities. The inhibitory effect on the proliferation of four human tumor cell lines (MCF-7, MDA-MB-231, MDA-MB-468 and A549) was observed. Among them, compound E1 exhibited the strongest inhibitory effect on the proliferation of MDA-MB-231 cells with an IC 50 value of 1.43 μM, which was significantly superior to that of Apcin. Further biological studies demonstrated that compound E1 inhibited cancer cell migration and colony formation. Furthermore, compound E1 specifically targeted CDC20 and exhibited a higher binding affinity to CDC20 compared to that of Apcin, thereby inducing cell cycle arrest in the G2/M phase of cancer cells. Moreover, it has been observed that compound E1 induces autophagy in cancer cells. In 4T1 Xenograft Models compound E1 exhibited the potential antitumor activity without obvious toxicity. These findings suggest that E1 could be regarded as a CDC20 inhibitor deserved further investigation. [Display omitted] • The compounds were designed as potential inhibitors for CDC20 based on Apcin. • All derivatives were tested for antiproliferative activities against cell lines. • Compound E1 has been proven to have in vivo antiproliferative activity. • Discovery of autophagy as a pathway for cell death in compound E1. [ABSTRACT FROM AUTHOR]

Abstract: Three new phenanthrenes, thrigonosomone A (1), 6,9-O-dedimethyltrigonostemone (2), and thrigonosomone B (3) were isolated from Trigonostemon lii. Their structures were elucidated by spectroscopic methods. Thrigonosomone A (1) possessed a novel seven-membered cyclic anhydride moiety, and its relative configuration was determined by chemical computation and ROESY experiment. The cytotoxicity of compounds 1–3 was also evaluated. [Copyright &y& Elsevier]

The formation of amyloid- β (A β) plaques in the brain is one of the main pathological features of Alzheimer's disease (AD). The imaging probes, capable of detecting A β deposition, are important tools for early diagnosis of AD. In this article, we designed, synthesized and evaluated a cyanine-based near-infrared fluorescence (NIRF) probe ZT-1 for the detection of A β deposits in the brain. The probe had excellent fluorescent properties with an emission maximum above 720 nm upon binding to A β aggregates with affinity of 445.0 nM (K d). Furthermore, ZT-1 exhibited good biostability, photostability, and binding selectivity toward A β 1-42 aggregates by in vitro fluorescence staining experiments. In vivo NIRF imaging result also revealed that our probe could efficiently differentiate transgenic and wild-type mice. All these studies indicated that ZT-1 is a promising fluorescent probe for A β plaques in the AD brains. Image 1 • A probe ZT-1 for the detection of A β deposits in the brain was synthesized and evaluated. • ZT-1 exhibited good biostability, photostability, and binding selectivity toward A β 1-42 aggregates. • ZT-1 could efficiently differentiate transgenic and wild-type mice by in vivo NIRF imaging. [ABSTRACT FROM AUTHOR]

Osteosarcoma is the most frequent malignant primary bone tumor, and it generally develops a multidrug resistance. Chrysanthemulide A (CA) is a sesquiterpenoid from the herb Chrysanthemum indicum that has demonstrated a great anti‐osteosarcoma potential. In this study, CA‐induced apoptotic cell death resulted in the activation of the caspase‐8‐mediated caspase cascade, as evidenced by the cleavage of the substrate protein Bid and the caspase‐8 inhibitor Z‐VAD‐FMK. The CA treatment upregulated the expression of death receptor 5 (DR5) in both whole cells and the cell membrane. Blocking DR5 expression by the small interfering RNA (siRNA) treatment decreased the caspase‐8‐mediated caspase cascade and efficiently attenuated CA‐induced apoptosis, suggesting the critical role of DR5 in CA‐induced apoptotic cell death. CA‐induced upregulation of the DR5 protein was accompanied by the accumulation of LC3B‐II, indicating the formation of autophagosomes. Importantly, DR5 upregulation was mediated by transcriptionally controlled autophagosome accumulation, as blockade of autophagosomes by LC3B or ATG‐5 siRNA substantially decreased DR5 upregulation. Furthermore, CA activated the c‐Jun N‐terminal kinase (JNK) signaling pathway, and treatment with JNK siRNAs or inhibitor SP600125 significantly attenuated CA‐mediated autophagosome accumulation and DR5‐mediated cell apoptosis. Finally, CA sensitized the osteosarcoma cells to the DR5 ligand tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL)‐induced apoptotic cell death. Above all, these results suggest that CA induces apoptosis through upregulating DR5 via JNK‐mediated autophagosome accumulation and that combined treatment with CA and TRAIL might be a promising therapy for osteosarcoma. [ABSTRACT FROM AUTHOR]

Twelve formyl phloroglucinol meroterpenoids (FPMs) were isolated from the leaves of Eucalyptus robusta Smith. Their structures were elucidated via spectroscopic data analysis, the circular dichroism (CD) exciton chirality method, Rh 2 (OCOCF 3) 4 -induced CD experiments, and application of the Snatzke chirality rules. Eucalrobusones Q, S, and X are the first FPMs that have been identified in which the C-7′ of phloroglucinol is linked to the C-15 of cadinane, the C-4 of cubebane, and the C-8 of menthane, respectively. (+)-Eucalrobusone X exhibited the most potent antifungal ability against Candida albicans with a MIC 50 value of 10.78 μ g/mL, and eucalrobusone U exhibited the greatest anti- C. glabrata activity with MIC 50 value of 1.53 μ g/mL. As a result of investigating antifungal formyl phloroglucinol meroterpenoids (FPMs), twelve FPMs including three undescribed carbon skeletons were isolated from the leaves of Eucalyptus robusta. Image 1 • Twelve formyl phloroglucinol meroterpenoids (FPMs) were isolated from Eucalyptus robusta. • The carbon skeletons of compounds 1 , 3 , 9 , and 10 are reported here for the first time. • FPMs were determined by CD exciton chirality method, Rh 2 (OCOCF 3) 4 -induced CD experiment, and the Snatzke chirality rules. • Some FPMs exhibited significant antifungal activities against Candida glabrata and C. albicans. [ABSTRACT FROM AUTHOR]

Hyperpatulols A–I, nine new spirocyclic acylphloroglucinol derivatives with anti-migration activities by regulating the expressions of Vimentin and E-cadherin to suppress the EMT process, were isolated from the flowers of Hypericum patulum. • Nine new spirocyclic acylphloroglucinol derivatives were obtained. • The anti-migration activities of all isolates were evaluated with U2-OS cells. • Hyperpatulol D (4) exhibited anti-migration activity by suppressing the EMT process. • This is the first research on the mechanism of the anti-migration activity of PPAPs. Nine new spirocyclic acylphloroglucinol derivatives, hyperpatulols A–I (1 – 9), were characterized from the flowers of Hypericum patulum. Their structures were elucidated by the basic analysis of the obtained spectroscopic data, and their absolute configurations were assigned by both the electronic circular dichroism (ECD) exciton chirality method and ECD calculation. The evaluation of their anti-migration effects on U2-OS human osteosarcoma cells showed that compound 4 exhibited moderate inhibitory activity in a dose-dependent manner. Further pharmacological studies revealed that 4 could regulate the expression of the proteins Vimentin and E-cadherin. [ABSTRACT FROM AUTHOR]