Noncovalent composites of meso-substituted A2B2-porphyrins and carbon nanotubes for enhanced electrocatalytic oxygen reduction.

Exploring highly active oxygen reduction electrocatalysts with low precious metals content is imperative but remains a considerable challenge. Herein, a series of heterobimetallic multi-walled carbon nanotubes (MWCNTs) electrocatalysts based on metal complexes are presented. These electrocatalysts feature diverse transition metals (M=Mn, Fe, Co, Ni) 5,15-bromophenyl-10, 20-methoxyphenyl porphyrin (MBMP) and tetrakis(triphenylphosphine)palladium (0) (Pd[P(Ph3)4]) anchored non-covalently on its surface. The resulting NiBMP-based MWCNTs with Pd[P(Ph3)4] (PdNiN4/MWCNTs) display outstanding electrocatalytic oxygen reduction activity (onset potential, 0.941 V; half wave potential, 0.830 V) and robust long-term durability in alkaline electrolyte. While in neutral condition, the MnBMP-based MWCNTs with Pd[P(Ph3)4] (PdMnN4/MWCNTs) are the most active heterobimetallic ORR catalyst and produce ultra-low concentration hydrogen peroxide (H2O2yield, 1.2%-1.3%). Synergistically tuning the ORR electrocatalytic activity and electron transfer pathway is achieved by the formation of NiBMP/MnBMP-Pd[P(Ph3)4] active sites. This work indicates such metalloporphyrin-Pd[P(Ph3)4] active sites on MWCNTs have significantly positive influence on electrocatalytic ORR systems and provides facile and mild strategy for designing highly efficient ORR electrocatalysts with ultra-low loading precious metal.

Isolation and identification of hemostatic steroidal glycosides from Ypsilandra thibetica.

The phytoconstituents of the fraction with hemostatic activity of the 70% aqueous ethanol extract of Ypsilandra thibetica Franch. were investigated. As a result, fourteen previously unreported spirostanol saponins, ypsilandrosides Z1-Z14, and nine known analogues were isolated and characterized by MS, NMR, and chemical methods. Among them, ypsilandrosides Z1-Z4 (1-4) have a rare 12-O-ß-d-glucopyranosyl group, while ypsilandrosides Z5-Z8 (5-8) possess a rare double bond between C-4 and C-5, and a hydroxyl or carbonyl located at the C-6. All isolates were further tested for their hemostatic activity. The results suggested that five spirostanol tetraglycosides show favorable inducing platelet aggregation activities. Among them, ypsilandroside G (16) displayed significant inducing platelet aggregation activity with an EC50 value of 57.17 µM. Furthermore, the preliminary structure-activity relationship of these spirostanol glycosides' hemostatic activity was discussed.

Establishment of LC-MS/MS Method for Determination of GMDTC in Rat Plasma and Its Application in Preclinical Pharmacokinetics.

Sodium (S)-2-(dithiocarboxylato((2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl)amino)-4(methylthio)butanoate (GMDTC) is the first compound to use cadmium repellent as an indication. In this paper, we established and validated a bioanalytical method for the determination of GMDTC in rat plasma, and used it to determine the drug concentrations in the plasma of rats after intravenous dosing in different genders and dosages. After pretreating the plasma samples with an acetonitrile-water-ammonia solution (70:30:1.25, v/v/v), liquid chromatographic separations were efficiently achieved with a XBridge C18 column using a 5 min gradient system of aqueous ammonium bicarbonate and 95% acetonitrile-water solution (95:5, v/v) as the eluent. The GMDTC and metolazone (internal standard, IS) detection were carried out using high-performance liquid chromatography coupled with triple quadrupole mass spectrometry (LC-MS/MS), monitored at m/z 390.06-324.1 (for the GMDTC, tR: 2.03 min) and m/z 366.0-259.2 (for IS, tR: 3.88 min). The GMDTC was stable under various testing conditions, and this analytical method conforms to the verification standard of biological analysis methods. The half-life (t1/2) was determined to be 0.54-0.65 h for the intravenous, mean distribution volume and clearances were 1.08-2.08 L/kg and 1-3 L/h/kg, respectively. The AUC0-t and AUC0-∞ found after increasing the dosage exhibited a linear relationship with the administered dose. There were no statistically significant differences in the values obtained for the different genders at dosages of 50, 100 and 250 mg/kg, respectively (p > 0.05). This is the first report of a bioanalytical method to quantify GMDTC in rat plasma using LC-MS/MS, which provides useful information for the study of its pharmacological effects and clinical applications.

Sarcanolides C-E: three new lindenane sesquiterpenoid dimers with anti-inflammatory activities from Sarcandra glabra.

Three new lindenane-type sesquiterpenoid dimers, sarcanolides C-E (1-3), were isolated from the roots of Sarcandra glabra. Sarcanolide C (1) possesses a unique decacyclic scaffold with an unusual orthoformate unit. The structures of 1-3 were determined through extensive spectroscopic analysis, while their absolute configurations were determined by comparison of calculated and experimental electronic circular dichroism (ECD) spectra. Compounds 1-3 were evaluated for their inhibitory activity against LPS-induced nitric oxide (NO) production in RAW264.7 macrophages. All the isolates displayed a moderate inhibitory effect against NO production with IC50 values in the range of 13.4-17.2 µM, comparable to that of the positive control L-NMMA.

Manganese corrole catalyzed selective oxidation of styrene to benzaldehyde: sodium nitrite functions as an oxidant and cocatalyst.

Catalytic oxidation using manganese corrole is a hot topic of contemporary porphyrin chemistry, in which PhIO, TBHP, PhI(OAc)2, KHSO5 and m-CPBA are usually used as oxidants. This article reports the first selective oxidation of styrene to benzaldehyde using a manganese(III) corrole catalyst and sodium nitrite (NaNO2) as oxidant and cocatalyst at room temperature. The yield was 158.1% in air and 96.5% under a nitrogen atmosphere, showing oxygen might be involved in the reaction and that NaNO2 is an oxygen source and cocatalyst in the system. The peripheral electron-withdrawing substituents of the manganese corrole were favorable to the catalytic reaction. Radical inhibition and H218O experiments proved that the catalytic reaction was a free radical and hydrolysis-involved reaction.

Photodynamic antitumor activity of Gallium(III) and Phosphorus(V) complexes of trimethoxyl A2B triaryl corrole.

Two new trimethoxyl A2B triaryl corroles 10-(2,4,6-trimethoxyphenyl)-5,15-bis(pentafluorophenyl)- corrole (1) and 10-(3,4,5-trimethoxyphenyl)-5,15-bis(pentafluorophenyl)-corrole (2) and their gallium(III) and phosphorus(V) (1-Ga, 1-P, 2-Ga and 2-P) complexes had been prepared and well characterized by UV-vis, NMR and HR-MS. Among all compounds, 2-Ga, 1-P and 2-P showed excellent in vivo photodynamic activity against the MDA-MB-231, A549, Hela and HepG2 cell lines upon light irradiation at 625 nm. And 2-P even exhibited higher phototoxicity than the clinical photosensitizer temoporfin. Also, 2-P exhibited the highest singlet oxygen quantum yield and photostability. The preliminary investigation revealed that 2-P could be rapidly absorbed by tumor cells and mainly located in the cytoplasm. After photodynamic therapy (PDT) treatment with 2-P, mitochondrial membrane potential destruction, intracellular ROS level increasing and nuclear fragmentation of cancer cells could be observed. Cell cycle analysis demonstrated that the 2-P PDT may cause tumor cell arrest at sub-G1 stage and induce early and late apoptosis of cells. These results suggest that 2-P is a promising candidate as a photosensitizer for photodynamic therapy.

Halogenated Gallium Corroles:DNA Interaction and Photodynamic Antitumor Activity.

A series of halogenated gallium corroles were synthesized and characterized by UV-vis, HRMS, NMR, and FT-IR. The interaction between these gallium corroles and calf thymus DNA had been investigated by spectroscopic methods. These gallium corroles would interact with CT-DNA via an outside binding mode. The photodynamic antitumor activity in vitro of these gallium corroles toward different cell lines had also been tested. 3-Ga displayed low cytotoxicity to normal cells under both light and dark conditions but high phototoxicity to liver cancer cells HepG2. The vitro experiment results showed that 3-Ga could be efficiently absorbed by tumor cells. After light illumination, it may induce reactive oxygen species (ROS) and cause destruction of the mitochondrial membrane potential, which may finally trigger tumor cell apoptosis. Flow cytometry results showed that HepG2 cells were mainly distributed in the sub-G0 phase, which corresponds to cells with highly fragmented DNA or dead cells generally. This suggests that 3-Ga could lead to tumor cell apoptosis after light illumination.

Acylphloroglucinol trimers from Callistemon salignus seeds: Isolation, configurational assignment, hAChE inhibitory effects, and molecular docking studies.

Alzheimer's disease (AD) diagnoses are greatly increasing in frequency as the global population ages, highlighting an urgent need for new anti-AD strategies. With the aim to search for human acetylcholinesterase (hAChE) inhibitors from the species of Myrtaceae family, ten acylphloroglucinol trimers (APTs), including eight new APTs, callistemontrimers A-H (1a, 1b, 2a, 2b, 3a, 3b, 4b, and 5b), and two naturally occurring ones (4a and 5a), along with one reported triketone-acylphloroglucinol-monoterpene adduct (6), were obtained and structurally characterized from the hAChE inhibitory acetone extract of Callistemon salignus seeds. The structures and their absolute configurations for new APTs were unequivocally established via the detailed interpretation of extensive spectroscopic data (HRESIMS and NMR), ECD calculations, and single crystal X-ray diffraction, whereas the absolute configurations of known APTs were determined by further chiral separation, and calculated ECD calculations. The results of hAChE inhibitory assay revealed that an enantiomeric mixture of 2a/2b, 2a, and 2b are good hAChE inhibitors with IC50 values of 1.22 ±â€¯0.23, 2.28 ±â€¯0.19, and 4.96 ±â€¯0.39 µM, respectively. Molecular docking was used to uncover the modes of interactions for bioactive compounds with the active site of hAChE. In addition, 2 and 6 displayed moderate neurite outgrowth-promoting effects with differentiation rates of 6.16% and 6.19% at a concentration of 1.0 µM, respectively.

Polymethylated acylphloroglucinols from Rhodomyrtus tomentosa exert acetylcholinesterase inhibitory effects.

Chemical investigation of the twigs and leaves of Rhodomyrtus tomentosa led to the isolation and structural identification of a novel polymethylated phloroglucinol meroterpenoid (PPM) featuring a 6/6/6/6 tetracyclic system, rhotomentodione F (1), five new polymethylated polycyclic phloroglucinols (PPPs) with a rare bis-furan framework, rhotomentosones A-E (2-6), and one new adduct composed of an acylphloroglucinol and two ß-triketone units, rhotomentosone F (7), as well as five known analogues (8-12). Their structures and absolute configurations were unambiguously determined by comprehensive spectroscopic data and electronic circular dichroism (ECD) calculations. All isolates were evaluated for their anti-inflammatory and acetylcholinesterase (AChE) inhibitory activities. Compound 6 displayed significant AChE inhibitory effect with an IC50 value of 8.68 µM. Further molecular docking studies of 6 revealed that the interactions with AChE residues Ser125, Glu202, and Tyr133 are crucial for AChE inhibitory activity. The current study not only enriches the chemical diversity of phloroglucinols in Myrtaceae species, but also provides potential lead compounds for the further design and development of new AChE inhibitors to treat Alzheimer's disease.

Non-volatile acylphloroglucinol components from Eucalyptus robusta inhibit Zika virus by impairing RdRp activity of NS5.

Eucalyptus is a large genus of the Myrtaceae family with high value in various fields of industry. Recently, attention has been focused on the functional properties of Eucalyptus extracts. These extracts have been traditionally used to combat various infectious diseases, and volatile oils are usually considered to play a major role. But the positive effects of non-volatile acylphloroglucinols, a class of specialized metabolites with relatively high content in Eucalyptus, should not be neglected. Herein, non-volatile acylphloroglucinols from leaves of Eucalyptus robusta were evaluated for their abilities to inhibit Zika virus (ZIKV) which is associated with severe neurological damage and complications. The results showed eucalyprobusone G, a new symmetrical acylphloroglucinol dimer, possessed the significant ability to inhibit ZIKV without inducing cytotoxicity. The EC50 values of eucalyprobusone G against the African lineage (MR766) and Asian lineage (SZ-WIV01) of ZIKV were 0.43 ± 0.08 and 10.10 ± 3.84 µM which were 110 times and 5.8 times better than those of the reference compound ribavirin, respectively. Further action mode research showed that eucalyprobusone G impairs the viral binding and RdRp activity of NS5. The results broaden the functional properties of Eucalyptus robusta and indicate acylphloroglucinol dimers could be developed as anti-ZIKV agents.

Resorcylic Acid Lactones Produced by an Endophytic Penicillium ochrochloron Strain from Kadsura angustifolia.

Four new ß-resorcylic acid lactones, including penochrochlactone A (2: ), 4-O-desmethyl-aigialomycin B (4: ), and penochrochlactones C and D (5: and 6: ), two compounds isolated from a natural source for the first time, 5α, 6ß-acetonide-aigialomycin B (1: ) and penochrochlactone B (3: ), together with six known compounds, aigialomycin F (7: ), aigialomycins A, B, and D (8: -10: ), zeaenol (11: ), and oxozeaenol (12: ), were isolated from a mycelial solid culture of the endophytic fungus Penicillium ochrochloron SWUKD4.1850 from the medicinal plant Kadsura angustifolia by sequential purification over silica gel, Sephadex LH-20 column chromatography, and preparative HPLC. Their structures were elucidated by extensive spectroscopic analysis and chemical conversions. In addition, all the new compounds were evaluated for their cytotoxic and antibacterial activities in vitro. Penochrochlactone C (5: ) displayed moderate cytotoxicity against the HeLa tumor cell line with an IC50 value of 9.70 µM. In the antibacterial assays, compounds 4:  - 6: exhibited moderate activities against Staphylococcus aureus, Bacillus subtilis, Escherichia coli, and Pseudomonas aeruginosa with MIC values between 9.7 and 32.0 µg/mL.

Robustadial A and B from Eucalyptus globulus Labill. and their anticancer activity as selective tyrosyl-DNA phosphodiesterase 2 inhibitors.

Tyrosyl-DNA phosphodiesterase 2 (TDP2) is a recently discovered DNA repair enzyme that can repair topoisomerase 2-mediated DNA damage, resulting in cancer cell resistance. In this study, two compounds, robustadial A and B, were isolated from a fraction of the ethyl acetate extract of Eucalyptus globulus Labill. fruits based on TDP2 inhibition screening. The biological experiments indicated that robustadial A and B have TDP2 inhibitory activity with EC50 values of 17 and 42 µM, respectively, but no tyrosyl-DNA phosphodiesterase 1 inhibition at 100 µM. Robustadial A showed significant synergistic effects with the anticancer drug etoposide in four human cancer cell lines, non-small cell lung cancer cell line (A549), prostate cancer cell line (DU145), breast cancer cell line (MCF-7), colorectal adenocarcinoma cell line (HCT-116), and chicken lymphoma cell line (DT40), and chicken lymphoma cell line complementation with human TDP2 (DT40 hTDP2) with combination index values ranging from 0.21 to 0.74. This work will facilitate future efforts for the development of robustadial A-based TDP2 selective inhibitors.

Phytochemicals from the Leaves of Cyclocarya paliurus and their 11ß-HSD1 Enzyme Inhibitory Effects.

Two new dammarane-type triterpenoid saponins, 3ß-(α-l-arabinopyranosyloxy)-24,25-dihydroxydammar-20-en-12α-yl 6-deoxy-ß-d-glucopyranoside (1) and (24R)-3ß-[(4-O-acetyl-α-l-arabinopyranosyl)oxy]-25-hydroxy-20,24-epoxydammaran-12ß-yl 6-deoxy-ß-d-glucopyranoside (2), and fourteen known triterpenoids were isolated from the 70 % MeOH extract of the leaves of Cyclocarya paliurus. Their structures were established based on analyses of spectroscopic data. All compounds were tested for their inhibitory activities against the 11ß-HSD1 enzyme. Hederagenin (13) exhibited moderate inhibitory effect for mouse 11ß-HSD1 with an IC50 value of 0.16±0.04 µM.

Acylphloroglucinols with acetylcholinesterase inhibitory effects from the fruits of Eucalyptus robusta.

Eleven new acylphloroglucinols, including six new formylated phloroglucinol-monoterpene meroterpenoids, eucalyprobusals A-F (1-6), one monomeric acylphloroglucinol, eucalyprobusone B (7), and four dimeric acylphloroglucinols, eucalyprobusones C-F (8-11) were purified from the fruits of Eucalyptus robusta. The establishment of the structures of 1-11 was achieved by a combination of NMR and HRESIMS data analyses, electron circular dichroism (ECD), and single-crystal X-ray diffraction. Compounds 6, 8, and an inseparable mixture of 10 and 11 were found to be potent AChE inhibitors with IC50 values of 3.22 ± 0.36, 3.82 ± 0.22, and 2.55 ± 0.28 µΜ, respectively. Possible interaction sites of 6, 8, 10, and 11 with AChE were investigated by means of molecular docking studies, and the results revealed that AChE residues Asn87, Ser125, Thr83, Tyr133, Tyr124, Tyr337, and Tyr341 played crucial roles in the observed activity of the aforementioned compounds.

Polyphyllosides A-F, six new spirostanol saponins from the stems and leaves of Paris polyphylla var. chinensis.

The first phytochemical investigation on the steroidal saponins from the stems and leaves of Paris polyohylla var. chinensis led to the discovery and characterization of six new spirostanol saponins, named polyphyllosides A-F (1-6), along with four known analogues (7-10). Their structures were unambiguously established via extensive spectroscopic data and chemical methods. Both polyphyllosides A and B had a rare aglycone with a C-4/C-5 double bond and a C-6 hydroxy group moiety, whereas polyphylloside C represents the first saponin with a unique aglycone sharing a C-6/C-7 double bond and a C-5 hydroxy group unit. All these saponins were evaluated for their cytotoxic activities against five selected human cancer cell lines. Among these, the known saponins 7 and 10 exhibited significant cytotoxic effects on HeLa cells with IC50 values of 4.16 and 4.45 µM, respectively. The structure-activity relationships (SAR) of these isolates were also discussed. Flow cytometric analysis indicated that 7 could induce MDA-MB-231 cell death in a concentration-dependent manner. Saponin 7 was proved to affect the cell cycle distribution and induced G2/M phase arrest in MDA-MB-231 cells.

Polymethylated Phloroglucinol Meroterpenoids from Rhodomyrtus tomentosa and Their Antibacterial and Acetylcholinesterase Inhibitory Effects.

Rhotomentodiones C-E, three new polymethylated phloroglucinol meroterpenoids with diverse configurations, were isolated from the twigs and leaves of Rhodomyrtus tomentosa. Their structures and absolute configurations were established mainly by means of comprehensive spectroscopic data and electron circular dichroism (ECD) calculation. Among them, Rhotomentodione D (2) exhibited both antibacterial activity with an MIC value of 12.5 µg/mL against Propionibacterium acnes and AChE inhibitory activity with an IC50 value of 22.9 µm.

Metal-Layer Assisted Growth of Ultralong Quasi-2D MOF Nanoarrays on Arbitrary Substrates for Accelerated Oxygen Evolution.

Controlled growth of metal-organic frameworks (MOFs) nanocrystals on requisite surfaces is highly desired for myriad applications related to catalysis, energy, and electronics. Here, this challenge is addressed by overlaying arbitrary surfaces with a thermally evaporated metal layer to enable the well-aligned growth of ultralong quasi-2D MOF nanoarrays comprising cobalt ions and thiophenedicarboxylate acids. This interfacial engineering approach allows preferred chelation of carboxyl groups in the ligands with the metal interlayers, thereby making possible the fabrication and patterning of MOF nanoarrays on substrates of any materials or morphologies. The MOF nanoarrays grown on porous metal scaffolds demonstrate high electrocatalytic capability for water oxidation, exhibiting a small overpotential of 270 mV at 10 mA cm-2 , or 317 mV at 50 mA cm-2 as well as negligible decay of performance within 30 h. The enhanced performance stems from the improved electron and ion transport in the hierarchical porous nanoarrays consisting of in situ formed oxyhydroxide nanosheets in the electrochemical processes. This approach for mediating the growth of MOF nanoarrays can serve as a promising platform for diverse applications.

Synthesis, characterization, and photodynamic therapy activity of 5,10,15,20-Tetrakis(carboxyl)porphyrin.

Water-soluble porphyrins are considered promising drug candidates for photodynamic therapy (PDT). This study investigated the PDT activity of a new water-soluble, anionic porphyrin (1-Zn), which possesses four negative charges. The photodynamic anticancer activity of 1-Zn was investigated by the MTT assay, with mTHPC as a positive control. The cellular distribution was determined by fluorescence microscopy. Holographic and phase contrast images were recorded after 1-Zn treatment with a HoloMonitor™ M3 instrument. The inhibition of A549 cell growth achieved by inducing apoptosis was investigated by flow cytometry and fluorescence microscopy. DNA damage was investigated by the comet assay. The expression of apoptosis-related proteins was also measured by western blot assays. 1-Zn had better phototoxicity against A549 cells than HeLa and HepG2 cancer cells. Interestingly, 1-Zn was clearly located almost entirely in the cell cytoplasmic region/organelles. The late apoptotic population was less than 1.0% at baseline in the untreated and only light-treated cells and increased to 40.5% after 1-Zn treatment and irradiation (P < 0.05). 1-Zn triggered significant ROS generation after irradiation, causing ΔΨm disruption (P < 0.01) and DNA damage. 1-Zn induced A549 cell apoptosis via the mitochondrial apoptosis pathway. In addition, 1-Zn bound in the groove of DNA via an outside binding mode by pi-pi stacking and hydrogen bonding. 1-Zn exhibits good photonuclease activity and might serve as a potential photosensitizer (PS) for lung cancer cells.

DNA interaction and photodynamic antitumor activity of transition metal mono-hydroxyl corrole.

A series of iron(III), manganese(III) and copper(III) mono-hydroxyl corrole complexes had been prepared and well characterized by UV-vis, 1H NMR, 19F NMR and HR-MS. These metallocorroles may bind to CT-DNA through external binding mode. Metallocorrole Fe-2c exhibited significant phototoxicity and low toxicity toward A549 tumor cells. While manganese (III) and copper (III) corroles showed hypotoxicity to A549, MCF-7 and HepG-2 tumor cells, whether under dark or illumination conditions. All tested metallocorroles exhibited non-toxicity to human normal cells (GES-1) with or without irradiation at 625 nm. Cell cycle analysis indicated that metallocorrole Fe-2c arrested the cell cycle at G2/M phase and increased the Sub-G1 phase in A549 cell lines. It was mainly localized at mitochondria and could significantly reduce mitochondrial membrane potential after photodynamic treatment, which would further induce tumor cell apoptosis.

The photocytotoxicity effect of cationic sulfonated corrole towards lung cancer cells: in vitro and in vivo study.

Corrole is a kind of new and promising photosensitizer (PS) in cancer photodynamic therapy (PDT). However, the protein molecular mechanism of PDT activity for corrole under light irradiation is still not clear. In this paper, water-soluble cationic sulfonated corrole (1) and its metal complexes (1-Fe, 1-Mn, and 1-Cu) were prepared, and the photodynamic anti-cancer activity against various tumor cells was investigated by MTT assay. The potential molecular mechanism of PDT activity was elucidated by fluorescence microscope, flow cytometry, molecular docking, and western blotting analysis. Besides, the potential PDT anti-tumor effect of 1 in vivo was assessed in human tumor xenografts in mice. Quantitative analysis revealed that 1's phototoxicity triggered a significant generation of reactive oxygen species, causing disruption of mitochondrial membrane potential. The results of western blotting (WB) assay shown in 1's phototoxicity could induce cell apoptosis via ROS-mediated mitochondrial caspase apoptosis pathway, in which SIRT1 protein degradation played a key role. PTD activity in vivo shown in 1 could significantly reduce the growth of A549 xenografted tumor, without obvious loss of mice body weight. We clearly found that cationic sulfonated corrole is a potential candidate of PS in vitro and in vivo. The phototoxicity of 1 could induce A549 cell apoptosis by inducing ROS production increase, further to activate the mitochondrial apoptosis pathway. We concluded that SIRT1 protein is a more appropriate target in this progress.