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Glass fibers (GFs)/epoxy laminated composites always present weak interlaminar shear strength (ILSS) and low cross-plane thermal conductivity coefficient (λ⊥). In this work, silica-sol, synthesized from tetraethyl orthosilicate (TEOS) and KH-560 via sol-gel method, was employed to functionalize the surface of GFs (Si-GFs). Together with a spherical boron nitride (BNN-30), the thermally conductive BNN-30/Si-GFs/epoxy laminated composites were then fabricated. Results demonstrate that Si-sol is beneficial to the improvement of mechanical properties for epoxy laminated composites (especially for ILSS). The BNN-30/Si-GFs/epoxy laminated composites with 15 wt% BNN-30 fillers display the optimal comprehensive properties. In-plane λ(λ//) and λ⊥ reach the maximum of 2.37 and 1.07 W·m−1·K−1, 146.9% and 132.6% higher than those of Si-GFs/epoxy laminated composites (λ// = 0.96 W·m−1·K−1 and λ⊥ = 0.46 W·m−1·K−1), respectively, and also about 10.8 and 4.9 times those of pure epoxy resin (λ// = λ⊥ 0.22 W·m−1·K−1). And the heat-resistance index (THRI), dielectric constant (ε), dielectric loss (tanδ), breakdown strength (E0), surface resistivity (ρs) as well as volume resistivity (ρv) are 197.3 °C, 4.95, 0.0046, 22.3 kV·mm−1, 1.8 × 1014Ω, and 2.1 × 1014Ω·cm, respectively. [ABSTRACT FROM AUTHOR]

Plants belonging to the genus Leonurus , also named motherwort, are traditionally used for anti-gynecological disorder in East Asia, and for sedative in Europe. Chemical investigation of the genus Leonurus not only enriched the natural products library, but also enlarged the pharmacological application of this traditional herb. In this review, we systematically summarized the structures of 259 compounds isolated from the genus Leonurus , featured with 147 labdane diterpenoids. The reported bioactivity studies up to 2017 are presented in the second part, with the main focus on the isolated compounds and also concerning the extracts. In addition to the traditional uterine contraction and sedative activity, recently the cardiovascular protection effect of leonurine has drawn most attention. Other than that, neuroprotection, anti-inflammation, anti-cancer, anti-platelet aggregation and many other activities have been assigned to various compounds from the genus Leonurus . Among 70 bioactivity references cited in this review, 57% of them were concentrated on two alkaloids (leonurine and stachydrine), whereas only 20% are about the 147 diterpenoids. Anti-inflammation is the major bioactivity discovered so far for the labdane diterpenoids from the genus Leonurus , whose further therapeutic potential still remains for exploration. [ABSTRACT FROM AUTHOR]

In recent years, shale gas has become an important energy source due to its abundant reserves. Due to their extremely tight initial properties, shale gas reservoirs require the use of the multi-stage fractured horizontal well (MFHW) technique to break the shale rock, activate closed natural fractures, and form a complex fracture network. In this study, to solve the issue of how to describe the fracture network's geometry and to predict the production performance accurately, a model that couples the fracture propagation with the fracturing fluid and proppant flow in a horizontal wellbore and hydraulic fractures is established. The displacement discontinuity method (DDM) and finite volume method are used to iteratively obtain numerical simulations of the fracture propagation. The accuracy of the fracture propagation model is verified through comparison with analytical and numerical models. Then, the coupled continuous media and discrete fracture network model considering multiscale flow mechanisms in shale is developed, which is solved numerically using the control volume finite element method (CVFEM) and unstructured tri-prism grids. Finally, the numerical simulation models are successfully applied to synthetic and field cases, sensitivity analysis is conducted to evaluate the influences of the proppant injection, stress anisotropy and distribution of the natural fractures on the fracture propagation and production performance of the MFHW in a shale gas reservoir. • The model couples the fracture propagation with fracturing fluid and proppant flow is established and solved. • The coupled continues media and discrete fracture network model is promoted, and solved by CVFEM and unstructured grids. • Sensitivity analysis is conducted to evaluate the influences on the fracture propagation and production performance. [ABSTRACT FROM AUTHOR]

A numerical method is employed to investigate the fluid flowing dynamics in fractured reservoirs in this paper. Owing to the multi-scales and strong heterogeneity, description of fracture network systems plays a significant role for a successful fractured reservoir simulation model. Comparing to previous works, this paper proposes a combination of dual continuum and discrete fracture network (DFN) model, which is used to simulate the flow in reservoirs with multi-scale fractures and proved feasible. In the first part of the paper, implicit flow equations of oil and water phase in fractured reservoirs are established to consider the nonlinearity properties. And then the control volume finite element method based on the unstructured grid system and N-R iteration are used to obtain the numerical solution. Moreover, the accuracy of this simulator is proved to be reasonable by field data; Sensitivity analysis shows that the existences of complex multi-scale fracture networks have great impacts on water flooding. Compared with the homogeneous reservoir, natural fracture (micro and large scale) networks can change the direction and velocity of the waterfront, which finally leads to the more serious water breakthrough, higher water cut and less recovery. The research and the numerical results obtained in this paper can provide theoretical guidance for efficient and scale development of natural fractured reservoirs. [ABSTRACT FROM AUTHOR]

In recent years, the greenhouse gas control has been a hot issue. A solution of injecting supercritical CO 2 (scCO 2) in Longmaxi shale gas formation (in Southwest China) is proposed in this study. To evaluate the feasibility of this method that storing CO 2 and enhanced gas recovery (EGR) simultaneously, we first carried out isothermal adsorption experiments on samples from Longmaxi formation to describe the adsorption behavior of CH 4 and CO 2 , and a generalized Ono-Kondo Lattice (OK) model was applied to predict adsorption amount of pure CH 4 /CO 2 and their binary mixtures under supercritical, high-pressure conditions. In addition, discrete fracture network (DFN) model was adopted to characterize the complex hydraulic fracture networks constructed from micro-seismic monitoring (MSM) data and engineering analysis. The porous flow in shale matrix was modeled with the multiple interacting continua (MINC) and fractal theories. A multiscale compositional numerical model based on unstructured tri-prism grids was finally developed and solved by control volume finite element (CVFE) method. The simulation results of base and CO 2 injection cases presented that scCO 2 huff 'n' puff in Longmaxi formation might be an effective method for CO 2 storage and EGR, and the orthogonal experiments were designed to optimize scenarios in the field application and obtain a maximum balanced result of EUR and CO 2 storage capacity (CSC) for multistage fractured horizontal well (MFHW) with complex fracture networks in shale. • The OK model was applied to predict pure CH 4 /CO 2 and their mixtures adsorption amount under supercritical conditions. • The hybrid DFN and MINC model was established to describe the flow in fractal porous media and complex fracture system. • The CVFE simulator was successfully conducted for comprehensive analysis of mechanisms of scCO 2 storage and EGR in shale. [ABSTRACT FROM AUTHOR]

Two new triterpenes mayteneri A (1), mayteneri B (2), and seven known compounds (3-9) were isolated from stems of Maytenus hookeri Loes. The chemical structures of compounds 1 and 2 were established by 1D, 2D NMR, HRESIMS analysis, and calculating electronic circular dichroism (ECD). The structures of known compounds 3-9 were determined by comparison of their spectral with those reported. Compounds 4-7 showed significant inhibitory activity for NLRP3 inflammasome, with the IC50 values of 2.36–3.44 μM. [ABSTRACT FROM AUTHOR]

Two new compounds, including a norsesquiterpenoid, annuionone H (1), and a quassinoid, picraqualide G (2), along with eleven known compounds (3–13), were isolated from the twigs and leaves of Picrasma quassioides. Comprehensive spectroscopic analyses and NMR calculation with DP4+ analysis were used to identify their structures. Moreover, of all these compounds, compound 4 showed a week inhibition rate in the anti-inflammatory screening results against mouse macrophage J774A.1 cell. [ABSTRACT FROM AUTHOR]

Two new compounds verboncin A (1) and verboncin B (4) and 14 known compounds (2–3 and 5–16) were isolated from Verbena bonariensis, and these 14 compounds were first obtained from this plant. Their chemical structures were established by one and two-dimensional NMR and HRESIMS analysis and the results were compared with literature values. The absolute configuration of 1 was determined by calculating electronic circular dichroism (ECD). The cytotoxicity of some of the compounds against MCF-7, HCT-116, MDA-MB-231, and SW620 human cancer cell lines were evaluated, in which compound 4 showed negligible cytotoxic activity with an IC50 value of 68.08 ± 0.35 µM against the MCF-7 cell line. [ABSTRACT FROM AUTHOR]

One new ionone glycoside, named centrantheroside F (1), together with 9 known compounds (2-10), were isolated from the roots of Centranthera grandiflora. Their structures were determined by spectroscopic data analyses and comparing with the literature data. The absolute configuration of 1 was confirmed via 2 D NMR and electronic circular dichroism (ECD). All isolated compounds were evaluated for their inhibitory activity on lipopolysaccharide (LPS)-induced nitric oxide (NO) production. [ABSTRACT FROM AUTHOR]

Vitex negundo var. Cannabifolia (Sieb. et Zucc.) Hand.-Mazz. leaves and twigs were used to isolate a new phenyldihydronaphthalene-type lignan (1) along with twenty known compounds. Comprehensive spectroscopic techniques such as UV, IR, NMR, HR-ESI-MS, ORD and ECD were used to identify their structures. Quantum chemical computations were used to assign the absolute configurations (AC) of (1). Using DP4+ analysis, the computed chemical shifts were used to pinpoint relative configuration. Compounds (1–6) were tested for biological activities. Compound (5) significantly decreased the release of lactate dehydrogenase (LDH) by 38% at a concentration of 10 μM, demonstrating that compound (5) had significant anti-inflammatory effects on the activation of the NLRP3 inflammasome, while no compound was found potent at a concentration of 200 μM against tyrosinase. Additionally, the chemotaxonomic significance of the isolated compounds was studied. [Display omitted] • One new phenyldihydronaphthalene-type lignan along with twenty known compounds from Vitex negundo var. Cannabifolia. • Spectroscopic analyses and quantum chemistry calculations were used to elucidate structures. • Compound 5 inhibited the release of lactate dehydrogenase (LDH) by 38% at a concentration of 10 μM. • Chemotaxonomic significance of the isolated compounds was discussed. [ABSTRACT FROM AUTHOR]

Nine previously undescribed clerodane-type diterpenoids (1–9), named caseabalanspenes A-I , along with six know compounds (10–15), were isolated from the twigs and leaves of Casearia velutina. Spectroscopic data (1D and 2D NMR) analysis permitted the definition of their structures and then determination of the molecular formula of the compound by high resolution mass spectrometry (HR-ESI-MS). It is worth noting that compound 7 contains N- heterocycle. Compounds 1–8 were tested the anti-inflammasome activity, and compound 3 exhibited potent activity and decreased LDH level in a dose-dependent manner, with IC 50 values of 2.90 μM. [Display omitted] • Nine undescribed clerodane diterpenoids were isolated from Casearia velutina. • Their structures were determined by 1D, 2D-NMR and HR-ESI-MS analyses. • The structure of compound 7 contains an N-heterocycle. • Compound 3 exhibited NLRP3-inflammasome inhibitory activity with IC 50 values of 2.90 μM. [ABSTRACT FROM AUTHOR]

[Display omitted] • Eleven new highly oxidized abietane diterpenoids were identified from Orthosiphon wulfenioides. • Compounds 1 – 4 , 6 and 8 exhibited potent inhibitory effects on NLRP3 inflammasome, and the IC 50 value of compound 1 was 0.23 μM. • Compound 1 inhibited cell pyroptosis via suppressing the expressions of Caspase-1 and IL-1β. Wulfenioidones A − K (1 – 11) were abietane diterpenoids with highly oxidized 6/6/6 aromatic tricyclic skeleton isolated from the whole plant of Orthosiphon wulfenioides , and their planar structures and absolute configurations were elucidated by spectroscopic data interpretation, electronic circular dichroism calculation as well as X-ray crystallography analysis. Bioactivity screening indicated that compounds 1 – 4 , 6 and 8 exhibited lactate dehydrogenase (LDH) inhibition effect with IC 50 values ranging from 0.23 to 3.43 μM by preventing the mononuclear macrophage cell pyroptosis induced by double signal stimulation of LPS and nigericin. Western Blot analyses of Caspase-1 and IL-1β down-regulation exhibited that compound 1 could selectively inhibit NLRP3 inflammasome, and the cell morphological observation further supported that compound 1 prevented macrophage cell pyroptosis. [ABSTRACT FROM AUTHOR]

Eleven undescribed 16,17-dinor-abietane diterpenoids, caseazins A-K (1 − 11), and ten known diterpenoids (12 − 21) were isolated from the twigs and leaves of Casearia kurzii (Flacourtiaceae). Caseazins A-K were the first abietane -type dinorditerpenoids to have been isolated from the plant of Casearia kurzii. Their chemical structures were elucidated using a combination of 1D and 2D NMR spectroscopy and mass spectrometry. The absolute configurations of 5 and 10 were established by electronic circular dichroism calculations. Moreover, compounds 2 , 3 , 13 , 14 , and 18 exhibited anti-inflammatory activity with IC 50 values of 0.17, 0.36, 6.55, 1.30, and 4.53 μM, respectively. IL-1β and caspase-1 analyses suggested that compound 14 inhibited NLRP3 inflammasome activation and blocked macrophage pyroptosis. Diterpenoids from Casearia kurzii with NLRP3 inflammasome inhibitory activity were reported in this research. [Display omitted] • Eleven undescribed dinorditerpenoids were isolated from Casearia kurzii. • The compound 14 showed potent inhibitory activity against pyroptosis by blocking NLRP3 inflammasome activation. Their structures were established by elucidated by NMR, HRESIMS and ECD analyses. [ABSTRACT FROM AUTHOR]

Fourteen undescribed seco -type diterpenoids, named nudifloids A-N, together with ten known analogs, were isolated from the leaves of Callicarpa nudiflora. Nudifloids A-N had a characteristic 3,4- seco -labdane-type diterpenoid skeleton, whereas nudifloids A-C and K–N were 3,4- seco -norditerpenoids. Nudifloid A was the first example of a 3,4- seco -12,13,14,15,16-quartnor-labdane diterpenoid, with a seven-membered lactone ring formed through esterification between C-3 and C-11. Nudifloids B and C were a pair of highly modified 3,4- seco -labdane nor-diterpenoid epimers, of which C-2 and C-18 were cyclized together to form a cyclohexene fragment. The structures of these undescribed diterpenoids were established by spectroscopic analysis and reference data. The anti-inflammatory activity of diterpenoids in rich yield was evaluated by analyzing the inhibition of lipopolysaccharide plus nigericin-induced pyroptosis in J774A.1 cells. Nudifloids D and E exhibited prominent anti-NLRP3 inflammasome activity, with IC 50 values of 1.80 and 1.59 μM, respectively. Cell permeability assays revealed that nudifloid D inhibited pyroptosis, which could ameliorate inflammation by blocking the activation of the NLRP3 inflammasome. Guiding by anti-inflammatory activity, fourteen undescribed 3,4- seco -labdane diterpenoids were isolated from the leaves of Callicarpa nudiflora , and evaluated the anti-inflammatory activity of abundant diterpenoids. [Display omitted] • Bioassay-guided isolation of C. nudiflora to obtain twenty-four seco -diterpenoids. • Of which, fourteen undescribed 3,4- seco -labdane diterpenoids were determined. • Nudifloid A exhibits the first example with a seven-numbered lactone ring. • Nudifloids D and E exhibited prominent inflammatory inhibitory activity. [ABSTRACT FROM AUTHOR]

[Display omitted] • Three unique ent -clerodane diterpenoid dimers were isolated from Callicarpa arborea. • The absolute configuration of 1 was deduced by single-crystal X-ray diffraction. • The absolute configuration of 2 and 3 was confirmed by NMR calculations with DP4 + analysis and ECD calculations. • The compound 2 and 3 showed potent cytotoxicity against MCF-7 and HCT-116 cell lines. Callicarpnoids A–C (1 – 3), three new ent -clerodane diterpenoid dimers formed via a [4 + 2] hetero Diels-Alder cycloaddition, appeared as a third example of this type of dimers, were isolated from the stems of Callicarpa arborea Roxb.. Their structures were elucidated by comprehensive spectroscopic analysis, and the absolute configurations were confirmed by single-crystal X-ray diffraction and electronic circular dichroism (ECD) calculations, as well as DP4 + analysis. Cytotoxicity test in two cell lines indicated that compounds 2 and 3 had significant cytotoxic effect against breast cancer cell (MCF-7) and colorectal cancer cell (HCT-116) with IC 50 ranging from 5.2 to 7.2 μ M, comparable to those of the positive control. Furthermore, the western blot analysis revealed that the protein expression levels of Bax were increased following compounds 2 and 3 treatment, whereas the expression levels of caspase 8, caspase 3, caspase 9 and Bcl 2 were decreased in a dose-dependent manner, indicating that compounds 2 and 3 may induce apoptosis via both intrinsic and extrinsic pathways in MCF-7 and HCT-116 cells. [ABSTRACT FROM AUTHOR]

[Display omitted] • 66 ent -clerodane diterpenoids, including 52 new compounds, were isolated from Callicarpa arborea. • Their bioactivity against pyroptosis were evaluated, and the typical α,β-unsaturated-γ-hemiacetal lactone ring was a key active segments from SAR analysis. • Compound 1 showed potent inhibitory activity against pyroptosis by blocking NLRP3 inflammasome activation. • Compound 1 treatment markedly reduced infiltration of CD11b+F4/80+ macrophages into lung and protected lung injury in LPS- induced septic mice. Pyroptosis is a programmed-inflammatory cell death, which leads to release of inflammatory cellular contents and formation of inflammation. Uncontrollable pyroptosis can result in serious immune diseases, such as cytokine release syndrome (CRS), sepsis, disseminated intravascular coagulation (DIC), and acute organ damage, including acute respiratory distress syndrome (ARDS) and acute kidney injury (AKI). Members of the Callicarpa genus are significant raw materials for traditional Chinese medicine, widely used for analgesia, hemostasis, and anti-inflammation. Previously, we have reported some ent -clerodane diterpenoids from Callicarpa arborea , shown potent inhibitory effects against pyroptosis. In this study, we went on investigating this kind of diterpenoids, and yielded 66 ent -clerodane diterpenoids, including 52 new compounds, from Callicarpa arborea. Their structures featured with a 5/6- (1 – 25) or a 6/6- (26 – 66)-fused double-ring scaffolds, were elucidated using spectroscopic data, electrostatic circular dichroism (ECD) and X-ray diffraction analyses. Screening for the inhibitory activity against pyroptosis by detecting of IL-1β secretion in J771A.1 cells, revealed 28 compounds with an IC 50 below 10.5 μM. Compound 1 was the most potent with an IC 50 of 0.68 μM and inhibited the J774A.1 macrophage pyroptosis by blocking the NLR pyrin domain containing 3 (NLRP3) inflammasome activation. An in vivo study further revealed that compound 1 decreased infiltration of CD11b + F4/80 + macrophages into lung and attenuated the lipopolysaccharide (LPS)-induced lung injury. Taken together, this study indicated the potential of compound 1 as a candidate for pyroptosis-related inflammation treatment, as well as provided the chemical and pharmacological basis for the further development of Callicarpa genus as a herbal medicine. [ABSTRACT FROM AUTHOR]

A phytochemical investigation to obtain bioactive substances as lead compounds or agents for anti-inflammatory led to the obtainment of eleven previously undescribed clerodane diterpenoids, named caseatardies A-K (1 − 11), and four known clerodane diterpenoids (12 – 15) from the twigs and leaves of Casearia tardieuae. The structural elucidation of these clerodane diterpenoids was based on 1D and 2D-NMR spectroscopy (COSY, HSQC, HMBC and ROESY) as well as high resolution mass spectrometry (HR-ESI-MS). The relative configurations were defined by ROESY correlations. The anti-inflammatory activity of all the isolated compounds was screened and compound 15 decreased LDH level in a dose-dependent manner, showing IC 50 value of 2.89 μM. [Display omitted] • Eleven new clerodane diterpenoids with conjugated diene side chain at C-9 were isolated from Casearia tardieuae. • The compound 15 showed potent inhibitory activity against pyroptosis by blocking NLRP3 inflammasome activation. • Their structures were established by elucidated by 1D, 2D-NMR and HR-ESI-MS analyses. [ABSTRACT FROM AUTHOR]

Ten new prenylated flavonoids, named denticulains A-J (1−10), together with seven known prenylated flavonoids (11–17) were isolated from Macaranga denticulata. Their structures were elucidated on the basis of detailed spectroscopic analysis and by comparison with literature data. In addition, compounds 1 and 14 inhibited the proliferation of SW620 and HCT-116 cell lines with an IC 50 value of 46.08 μM and 56.83 μM, respectively. [Display omitted] • Ten new prenylated flavonoids were isolated from Macaranga denticulata. • Some compounds have week anticancer activities. [ABSTRACT FROM AUTHOR]

[Display omitted] • Discovery of potent biaryl pyridine analogues and the most active RSK inhibitor was compound 7d , which shows similar RSK inhibitory efficacy to the lead compound LJH685. • Except for 7d, the compounds with higher activity all carry a benzyl group. • Molecular docking results show that 7d validates our molecular design. • Preliminary SAR and molecular models of selected compounds are studied. In order to discover and develop the new RSK kinase inhibitor, 50 pyridyl biaryl derivatives were designed and synthesized with LJH685 as the lead compound and their anti-tumor ability was tested. The results showed that the ability of 7d compound to inhibit the phosphorylation of YB-1 was comparable to that of LJH685. Among them, after preliminary screening, compound 7d showed good activity in inhibiting cell proliferation. Therefore, we took 7d as an example and performed molecular docking analysis on it. Judging from the overlapping combination diagram with LJH685, the results have verified that compound 7d has a similar skeleton to LJH685 and has a similar docking effect with RSK. Therefore, compound 7d is in line with the RSK inhibitor we designed and could be developed to a promising anti-tumor drug in the future. [ABSTRACT FROM AUTHOR]

A phytochemical investigation was conducted on Euphorbia helioscopia , resulting in the isolation of thirteen compounds, including nine undescribed diterpenoids, Euphzycopias A − I (1 – 9), of which the skeletons of compounds 1 – 4 were found in E. helioscopia L. Compounds 1 – 3 had 5/7/6 cyclic systems, while compound 4 had a 4/11 polycyclic system with a 4,7-cyclic ether between C-4 and C-7. The anti-inflammasome test using the isolated compounds (1–6, 8–13) showed that the diterpenes from E. helioscopia L. had a strong inhibitory effect on NLRP3 inflammasomes with IC 50 values of 3.34–14.92 μM. [Display omitted] • Nine undescribed diterpenoids were isolated from Euphorbia helioscopia L. • The skeletons of the first four compounds first appeared in the genus Euphorbia L. • Some compounds had significant anti-inflammatory activity on NLRP3 inflammasome. [ABSTRACT FROM AUTHOR]

Duan Teng Yimu decoction is a Chinese herbal medicine compound with proven therapeutic effects on inflammasome-related diseases, such as rheumatoid arthritis. This decoction consists of three Chinese herbal medicines, including Leonurus japonicus (L. japonicus), which promotes the blood circulation and exhibits detumescence activity, traditionally curing gynecologic and inflammasome diseases. To explore the anti-inflammasome activity and the underlying mechanisms of action of the compounds from L. japonicus. A series of compounds were isolated from L. japonicus. Their anti-inflammasome activities were evaluated in macrophages that were co-stimulated by lipopolysaccharide (LPS) and NLRP3 inflammasome inducers. NLRP3 inflammasome formation and apoptosis speck like containing a CARD (ASC) oligomerization were evaluated by immunofluorescent microscopy and Western blot analysis. The regulation of autophagy after treatment of this compound was also evaluated. Lastly, in vivo activity of Leojaponin was analyzed in a mouse acute gouty arthritis model. Here we show that Leojaponin, a diterpenoid compound from L. japonicus , suppressed lactate dehydrogenase and IL-1β release in Nigericin-stimulated macrophages in a pyroptosis model. Leojaponin inhibits NLRP3 inflammasome activation in both J774A.1 cells and bone marrow-derived macrophages in a dose dependent manner. Moreover, Leojaponin suppressed NLRP3-mediated ASC specks formation and ASC oligomerization. These activities of Leojaponin depend on restoration of autophagy via promoting RAPTOR phosphorylation. Furthermore, Leojaponin ameliorated monosodium urate (MSU)-induced acute gouty arthritis in vivo. Our findings suggest that Leojaponin inhibits NLRP3 inflammasome activation through enhancing autophagy via RAPTOR phosphorylation, thereby highlighting Leojaponin as a potent drug for inflammasome-related diseases. [Display omitted] [ABSTRACT FROM AUTHOR]

Nine undescribed limonoids, 18(13 → 14)- abeo -15β,21-dihydroxy-24,25,26,27-tetranor-3,7-dioxoapotirucalla-1,9(11),13(17),20(22)-tetraen-23,21-olide (Toonaone A), 21-hydroxy-24,25,26,27-tetranor-3,7,15-trioxoapotirucalla-1,9(11),20(22)-trien-23,21-olide (Toonaone B), 7α,21-dihydroxy-12α-isobutyryl-24,25,26,27-tetranor-3,15-dioxoapotirucalla-1,20(22)-dien-23,21-olide (Toonaone C), 7,8- seco -7-methyl ester-11β-acetoxy-14β,15β-epoxy-21-hydroxy-24,25,26,27-tetranor-3-oxoapotirucalla-1,8(30),20(22)-trien-23,21-olide (Toonaone D), 7,8- seco -7-methyl ester-11β-acetoxy-14β,15β-epoxy-23-hydroxy-24,25,26,27-tetranor-3-oxoapotirucalla-1,8(30),20(22)-trien-21,23-olide (Toonaone E), 7,8- seco -7-methyl ester-11β-acetoxy-14β,15β-epoxy-6β,21-dihydroxy-24,25,26,27-tetranor-3-oxoapotirucalla-1,8(30),20(22)-trien-23,21-olide (Toonaone F), 7,8- seco -7-methyl ester-14β,15β-epoxy-8α,21-dihydroxy-24,25,26,27-tetranor-3-oxoapotirucalla-1,20(22)-dien-23,21-olide (Toonaone G), 7,8- seco -7-methyl ester-14β,15β-epoxy-6β,8α,21-trihydroxy-24,25,26,27-tetranor-3-oxoapotirucalla-1,20(22)-dien-23,21-olide (Toonaone H), 7,8- seco -7-methyl ester-14β,15β-epoxy-6β,8α,21-trihydroxy-24,25,26,27-tetranor-3-oxoapotirucalla-1,20(22)-dien-21,23-diimide (Toonaone I), and five known analogues were isolated from the twigs of Toona ciliata M. Roem. (Meliaceae). Toonaone A possesses the first rare 18(13 → 14)- abeo -limonoid skeleton reported from the genus Toona. Their structures were elucidated using spectroscopic data analyses and quantum chemistry calculations. Biological evaluation showed that toonaone C, toonaone D, toonaone G, toonaciliatavarin F, and toonaciliatavarin G exhibited significant anti-NLRP3 inflammasome activity with IC 50 values ranging from 3.74 to 18.7 μM. GMDMD, IL-1β, and caspase-1 analyses suggested that toonaone D inhibited NLRP3 inflammasome activation and blocked macrophage pyroptosis. [Display omitted] • Nine undescribed limonoids and five analogues were isolated from of Toona ciliate. • Toonaone A possesses a rare 18(13. → 14)-abeo-limonoid skeleton. • Spectroscopic analyses and quantum chemistry calculations were used to elucidate structures. • Some compounds could significantly inhibit NLRP3 inflammasome activation. [ABSTRACT FROM AUTHOR]

• Twenty-four new limonoids were obtained from Toona ciliata. • Their structures were determined by spectroscopic analysis, quantum chemistry calculations, and X-ray diffraction. • Several compounds showed significant anti-NLRP3 inflammasome activity. Twenty-four new limonoids, toonaolides A−X (1 – 24), characterized with an α , β -unsaturated- γ -lactone A-ring were isolated from the twigs of Toona ciliata. Their structures and absolute configurations were elucidated by spectroscopic data, X-ray diffraction crystallography, and quantum chemistry calculations. Most of the isolated compounds (except 9 , 18 , and 24 which possessed the maleimide ring) featured the rare 21-hydroxybutenolide or 23-hydroxybutenolide moieties. In particular, compound 1 has an unprecedented limonoid architecture with 6/6 cis -fused A/B ring system and 2 has an unusual tetrahydrofuran ring B skeleton, featuring a 7/5/6/5 ring system. The biological evaluation showed that compounds 9 , 11 , 12 , 14 , and 18 exhibited significantly anti-NLRP3 inflammasome activity with IC 50 values ranging from 3.2 to 9.7 μM. Analysis of IL-1 β and caspase-1 expression revealed that compounds 11 and 12 are selective inhibitors of NLRP3 inflammasome, which could ameliorate cell pyroptosis by blocking NLRP3 inflammasome activation. [ABSTRACT FROM AUTHOR]

• A novel series of S -DABO derivatives have been designed and synthesized. • Selected compounds displayed potent activity against different HIV-1 strains. • Compound 5r only showed inhibition of HIV-1 DPDP activity unlike classical NNRTIs. • Preliminary SAR and molecular modeling of these novel congeners were investigated. In order to discover and develop the new HIV-1 NNRTIs, a series of 5-alkyl-6-(benzo[d][1,3]dioxol-5-ylalkyl)-2-mercaptopyrimidin-4(3H)-ones was synthesized and screened for their in vitro cytotoxicity against HIV-1. Most of the compounds we synthetized showed high activity against wild-type HIV-1 strain (IIIB) while IC 50 values are in the range of 0.06–12.95 μM. Among them, the most active HIV-1 inhibitor was compound 6-(benzo[d][1,3]dioxol-5-ylmethyl)-5-ethyl-2-((2-(4-hydroxyphenyl)-2-oxoethyl)thio)pyrimidin-4(3H)-one (5b) , which exhibited similar HIV-1 inhibitory potency (IC 50 = 0.06 μM, CC 50 = 96.23 μM) compared with nevirapine (IC 50 = 0.04 μM, CC 50 >200 μM) and most of compounds exhibited submicromolar IC 50 values indicating they were specific RT inhibitors. The compounds 5b , 6-(benzo[d] [1,3]dioxol-5-yl)-5-ethyl-2-((2-(4-hydroxyphenyl)-2-oxoethyl)thio)pyrimidin-4(3H)-one (5c) and 4-(2-((4-(benzo[d][1,3]dioxol-5-ylmethyl)-5-ethyl-6-oxo-1,6-dihydropyrimidin-2-yl)thio)acetyl)phenylbenzo[d][1,3]dioxole-5-carboxylate (5r) were selected for further study. It was found that all of them had little toxicity to peripheral blood mononuclear cell (PBMC), and had a good inhibitory effect on the replication of HIV-1 protease inhibitor resistant strains, fusion inhibitor resistant strains and nucleosides reverse transcriptase inhibitor resistant strains, as well as on clinical isolates. Besides, compound 5b and 5c showed inhibition of HIV-1 RT RNA-dependent DNA polymerization activity and DNA-dependent DNA polymerization activity, while compound 5r only showed inhibition of HIV DNA-dependent DNA polymerization activity, which was different from classical reverse transcriptase inhibitors. Our study which offered the preliminary structure-activity relationships and modeling studies of these new compounds has provided the valuable avenues for future molecular optimization. [ABSTRACT FROM AUTHOR]