(+)- and (-)-Tedanine, a pair of new enantiomeric indolone alkaloids from the marine sponge Tedania sp.

(+)- and (-)-Tedanine [(+)-1 and (-)-1], a pair of new enantiomeric indolone alkaloids, along with nine compounds (2-10) were isolated from the marine sponge Tedania sp. The structures of (+)-1 and (-)-1 including absolute configurations were determined by spectroscopic analysis and quantum chemical calculation. Compounds (+)-1 and (-)-1 were the first examples of indolone alkaloids isolated from this genus. In addition, the cytotoxic and antibacterial activities of these compounds were also evaluated.

Spongimides A and B, two new alkaloids from the marine sponge Spongia sp.

Two new alkaloids, spongimides A (1) and B (2), along with five known ones (3-7), were isolated from the marine sponge Spongia sp. The structures of 1 and 2 were determined by the spectroscopic methods (UV, IR, MS, and NMR) and X-ray diffraction analysis. Compounds 1, 3, and 4 were the first examples of 2,4-imidazolidinediones isolated from this genus. In addition, the cytotoxic and antibacterial activities of compounds 1 and 2 were also evaluated.

High-efficiency treatment of electroless nickel plating effluent using core-shell MnFe2O4-C@Al2O3 combined with ozonation: Performance and mechanism.

Heterogeneous catalytic ozonation (HCO) has been widely applied for the treatment of wastewater. In order to maintain the structural stability and surface catalytic activity of heterogeneous catalysts during the HCO treatment of electroless nickel plating effluent (ENPE), a MnFe2O4-C@Al2O3 catalyst with a core-shell structure was synthesized. MnFe2O4-C@Al2O3 was characterized and applied in the removal of total nickel (TNi) and organic contaminants from actual ENPE, using a coupled system of HCO combined with a magnetic dithiocarbamate chelating resin (MnFe2O4-C@Al2O3/O3-MDCR). Results show that embedding Al2O3 with C and MnFe2O4 significantly increased the TNi removal efficiency (99.3%), enhanced the O3-utilization efficiency and improved the generation of reactive oxygen species (ROS). The reaction rate (k = 0.7641 min-1) and O3-utilization efficiency established for TNi removal (ΔTNi/ΔO3 =0.221) by the MnFe2O4-C@Al2O3/O3-MDCR system, were 220% and 140% higher than the Al2O3/O3-MDCR system, respectively. Catalytic mechanism analysis demonstrated that surface hydroxyl groups, oxygen vacancy, metals, the carbon surface and its functional groups, can all potentially serve as catalytic active sites, with 1O2 and •OH considered to the predominant ROS. Overall, these findings verify that the synthesized MnFe2O4-C@Al2O3 catalyst possesses excellent catalytic capabilities and outstanding structural stability, making it suitable for practical application in the treatment of wastewater effluent.

Synthesis of Marine Cyclopeptide Galaxamide Analogues as Potential Anticancer Agents.

In this paper, eight new galaxamide analogues (Z-1~Z-8) were synthesized and evaluated for their cytotoxic activities against five cancer cell lines, MCF-7, MD-MBA-231, HepG2, Hela, and A549, using MTT assays. The modified analogue Z-6 displayed broad spectrum cytotoxic activity toward each tested cell line with IC50 values of 1.65 ± 0.30 (MCF-7), 2.91 ± 0.17 (HepG2), 4.59 ± 0.27 (MD-MBA-231), 5.69 ± 0.37 (Hela), and 5.96 ± 0.41 (A549) µg/mL, respectively. The galaxamides Z-3 and Z-6 induced concentration-dependent apoptosis of the MCF-7 cells after 72 h as evaluated by the flow cytometry experiment. The results showed that these compounds could induce MCF-7 cell apoptosis by arresting the G0/G1 phase of the cell cycle and finally achieving the effect of inhibiting the proliferation of MCF-7 cells.

Feasibility of reduced iron species for promoting Li and Co recovery from spent LiCoO2 batteries using a mixed-culture bioleaching process.

The recovery of metals from spent LiCoO2 batteries (SLBs) is essential to avoid resource wastage and the production of hazardous waste. However, the major challenge in regard to recovering metals from SLBs using traditional bioleaching is the low Co yield. To overcome this issue, a mixed culture of Acidithiobacillus caldus and Sulfobacillus thermosulfidooxidans was designed for use in SLBs leaching in this study. With the assistance of Fe2+ as a reductant, 99% of Co and 100% of Li were leached using the above mixed-culture bioleaching (MCB) process, thus solving the problem of low metal leaching efficiency from SLBs. Analysis of the underlying mechanism revealed that the effective extraction of metals from SLBs by the Fe2+-MCB process relied on Fe2+-releasing electrons to reduce refractory Co(III) to Co(II) that can be easily bioleached. Finally, the hazardous SLBs was transformed into a non-toxic material after treatment utilizing the Fe2+-MCB process. However, effective SLBs leaching was not achieved by the addition of Fe0 to the MCB system. Only 25% Co and 31% Li yields were obtained, as the addition of Fe0 caused acid consumption and bacterial apoptosis. Overall, this study revealed that reductants that cause acid consumption and harm bacteria should be ruled out for use in reductant-assisted bioleaching processes for extracting metals from SLBs.

Bioleaching for detoxification of waste flotation tailings: Relationship between EPS substances and bioleaching behavior.

The production of large volumes of waste flotation tailings results in environmental pollution and presents a major ecological and environmental risk. This study investigates bioleaching of waste flotation tailings using Acidithiobacillus ferrooxidans. The experiments were performed with 5.00% solid concentration, pH 2.0 with 100 mL medium for 25 d in the lab. The pH, OPR, metal concentration, dissolved organic matter (DOM) in leachate and extracellular polymeric substances (EPS) were recorded. Bioleaching tailing materials were finally characterized. Results showed that microorganisms, acclimating with mine tailings, effectively accelerated the bioleaching process, achieving maximum Zn and Fe extraction efficiencies of 95.45% and 83.98%, respectively, after 25 days. Compared with raw mine tailings, bioleaching could reduce 96.36% and 95.84% leachable Zn and Pb, and Pb presented a low risk (4.13%), while Zn, Cu, and Cr posed no risk (0.34%, 0.64%, and 0%). Toxicity and environmental risk analysis revealed bioleaching process significantly reduced the environmental risk associated with mine tailings. EPS analysis indicated that the loosely-bound EPS (LB-EPS) and tightly-bound EPS (TB-EPS) fractions contained different organic substances, which played different roles in the bioleaching process. Pearson correlation analysis revealed that EPS was highly correlated with bioleaching behavior (p < 0.05), and EPS was the main factor affecting the bioleaching process, promoting bioleaching in the LB-EPS and TB-EPS fractions.

(+)- and (-)-Spongiterpene, a pair of new valerenane sesquiterpene enantiomers from the marine sponge Spongia Sp.

(+)- and (-)-Spongiterpene [(+)-1 and (-)-1], a pair of new valerenane sesquiterpene enantiomers, along with four known compounds (2-5) were isolated from the marine sponge Spongia sp. The structures of (+)-1 and (-)-1 including absolute configurations were determined by spectroscopic analysis, quantum chemical calculation and X-ray diffraction. Compounds (+)-1 and (-)-1 were the first examples of valerenane sesquiterpenes isolated from the marine sponges. The cytotoxic activities of (+)-1 and (-)-1 were also evaluated.

High-level waste activated sludge dewaterability using Fenton-like process based on pretreated zero valent scrap iron as an in-situ cycle iron donator.

A novel, recyclable, and rapid pre-ultrasound-thermal-acid-washed zero valent scrap iron/hydrogen peroxide (UTA-ZVSI/H2O2) method has been developed to effectively enhance waste activated sludge (WAS) dewaterability. The effects of UTA ultrasound densities, UTA temperature, newly generated iron solution, H2O2 concentrations, and WAS conditioning time on the WAS dewaterability were investigated using a bench-scale system. Results indicated that the UTA-ZVSI/H2O2 treatment significantly improved the WAS dewaterability. The water content of the dewatered cake decreased to 44.15 ± 0.98 wt% during optimal operational conditions, which was significantly lower than that achieved using Fenton-based processes. Based on this outcome, a three-step treatment mechanism involving UTA-ZVSI/H2O2 has been developed, including iron flocculation, hydroxyl radical oxidation, and skeleton building. The dewatering efficiencies of three types of representative WAS were consistently effective in the UTA-ZVSI/H2O2 reactor for up to 15 cycles. Efficiencies levels were significantly higher than those achieved with Fenton-based processes. Economic analysis illustrated that the developed UTA-ZVSI/H2O2 system was the most cost-effective among other WAS dewatering treatments. In addition, the treatment system significantly alleviated toxicity of heavy metals and phytotoxicity in the dewatered sludge. This supported subsequent agricultural use. In summary, this study provided a comprehensive and useful basis for improving WAS dewatering and subsequent disposal.

Sinulaspirolactam A, a novel aza-spirocyclic valerenane sesquiterpenoid from soft coral Sinularia sp.

A novel valerenane sesquiterpenoid sinulaspirolactam A (1), together with five known compounds, was isolated from the soft coral Sinularia sp. Their structures were determined by spectroscopic analyses. The absolute configuration of 1 was established by ECD calculation. Compound 1 was the first example of valerenane sesquiterpenoid bearing an aza-spiro[4.5] ring moiety, the plausible biogenetic pathway of which was proposed. Cytotoxic activities of these compounds were also evaluated.

Synthesis and Biological Evaluation of Reniochalistatins A-E and a Reniochalistatin E Analogue.

The total synthesis of reniochalistatins A-E, along with a reniochalistatin E analogue (inverso-E) was successfully achieved through Fmoc-based solid-phase peptide synthesis and subsequent macrolactamization with PyBOP and DIEA. The biological activities of these reniochalistatins and a key linear peptide intermediate were systematically evaluated. Among these seven synthesized compounds, linear reniochalistatin B was found to have potent activity against several cancer cell lines not shown by the cyclic reniochalistatin B counterpart. In addition, linear reniochalistatin B was found to have antitubercular activity (IC50 =1.4 µm). Inverso-E possesses increasing cytotoxicity against the HeLa and LNCaP cell lines after simple alternation of the sequence of amino acids in reniochalistatin E. The results of these studies provide a feasible method to further investigate the structure-activity relationships (SARs) of reniochalistatins A-E.

Asperitaconic acids A-C, antibacterial itaconic acid derivatives produced by a marine-derived fungus of the genus Aspergillus.

Three new itaconic acid derivatives, asperitaconic acids A-C (1-3), were isolated from the ethyl acetate extracts of the rice fermentation of a marine-derived fungus Aspergillus niger, and asperitaconic acids A-C were characterized by an itaconic acid unit and an alkyl chain moiety. Their structures were established by interpretation of their spectroscopic data including NMR and HRESIMS. Asperitaconic acids A-C exhibited antibacterial effect against Staphylococcus aureus with MIC values of 16-32 µg/mL, whereas these compounds showed no cytotoxicity against HepG2 and HeLa cancer cell lines.

Antineoplastic activity of linear leucine homodipeptides and their potential mechanisms of action.

Galaxamide is a rare cyclic homopentapeptide composed of three leucines and two N-methyl leucines isolated from marine algae Galaxaura filamentosa. The strong antitumor activity of this compound makes it a promising candidate for tumor therapy. The synthesis of galaxamide, however, is a complex process, and it has poor water solubility. On the basis of its special chemical composition, we designed a series of linear leucine homopeptides. Among seven dipeptide derivatives, five compounds with terminal protection groups and methyl substitution of the hydrogen in the amido group showed remarkable inhibitory effects against various cancer cells. N-tertbutyl-D-leucine-N-methyl-D-leucinebenzyl (A7), the only stereomer condensed by two D-leucines, showed the highest antineoplastic activity. A7-treated cells showed cell cycle arrest and morphological changes typical of cells undergoing apoptosis. The population of Annexin-V positive/propidium iodide-negative cells also increased, indicating the induction of early apoptosis. A7 promoted the cleavage of caspase-9 and caspase-3, as well as increased intracellular Ca levels and decreased the mitochondrial membrane potential. Collectively, certain linear leucine dipeptides derived from cyclic pentapeptide are able to inhibit tumor cell proliferation through cell cycle arrest and apoptosis induction. The N-methyl group in the side chain and the D/L conformation of the amino-acid residue are critical for their activity.

A new α-pyrone from the deep-sea actinomycete Nocardiopsis dassonvillei subsp. dassonvillei DSM 43111(T).

A new α-pyrone, nocapyrone S (1), together with five known compounds (2-6), were isolated from the deep-sea actinomycete Nocardiopsis dassonvillei subsp. dassonvillei DSM 43111(T). Their structures were determined by spectroscopic analyses. The absolute configuration of 1 was established by quantum approaches. Cytotoxic activity of 1 was evaluated against K562, MCF-7, SGC7901, A375, Hela, and HepG2 cell lines.

d-Amino Acid Position Influences the Anticancer Activity of Galaxamide Analogs: An Apoptotic Mechanism Study.

Galaxamide, an extract from Galaxaura filamentosa, is a cyclic pentapeptide containing five l-leucines. Due to the particular cyclic structure and the excellent anticancer activity, synthesis of Galaxamide and its analogs and their subsequent bio-applications have attracted great attention. In the present work, we synthesized six Galaxamide analogs by replacing one of the l-leucines with phenylalanine and varying the d-amino acid position. The anticancer effect of the synthesized Galaxamide analogs was tested against four in vitro human cancer cell lines, human hepatocellular cells (HepG2), human breast cancer cell (MCF-7), human breast adenocarcinoma cells (MDA-MB-435) and a human cervical carcinoma cell line (Hela). Results showed that Galaxamide analogs with different d-amino acid positions displayed distinct anticancer potential. The Galaxamide analog containing d-amino acid at position 5 (Analog-6) presented the strongest anticancer activity. The mechanism study revealed that Analog-6 could cause the early apoptosis of HepG2 cells by inhibiting their growth in the sub-G1 stage of the cell cycle and induce the chromatin condensation and fragmentation, which can be seen as 68% of HepG2 cells inhibited in the sub-G1 stage. Moreover, a mitochondria-mediated pathway was found to be involved in the apoptotic process of Analog-6 on HepG2 cells.

Structurally diverse secondary metabolites from a deep-sea-derived fungus Penicillium chrysogenum SCSIO 41001 and their biological evaluation.

Five new compounds, including a cytotoxic dimeric isocoumarin, bipenicilisorin (1), a merosesquiterpenoid, yaminterritrem C (2), a citrinin dimer, penicitrinone F (3), a alkaloid, terremide D (4), and a δ-valerolacton, (E)-4-(propen-1-yl)-5,6-dihydro-2H-pyran-2-one (5), along with ten known compounds (6-15) were isolated from a deep-sea-derived fungus Penicillium chrysogenum SCSIO 41001. Their structures and absolute configurations were elucidated by NMR spectra, MS, CD, optical rotation, X-ray crystallography, and compared with literature data. Biological evaluation results revealed that 1 exhibited significant cytotoxic activities against K562, A549, and Huh-7 cell lines with IC50 values of 6.78, 6.94, and 2.59µM, respectively. Compound 3 exhibited moderate inhibitory activity against EV71 with IC50 value of 14.50µM. In addition, 13 and 14 showed specific COX-2 inhibitory activities with IC50 values of 1.09 and 1.97µM, respectively.

Cytotoxicity Study of Cyclopentapeptide Analogues of Marine Natural Product Galaxamide towards Human Breast Cancer Cells.

Herein, we report the cytotoxicity of cyclopentapeptide analogues of marine natural product galaxamide towards breast carcinoma cells and the underlying mechanisms. We examined the effect of the novel galaxamide analogues on cancer cell proliferation by MTT assay and also further examined the most active compound for morphological changes using Hoechst33342 staining technique, induction of apoptosis, cell cycle phases, mitochondrial membrane potential (MMP), and reactive oxygen species (ROS) generation using flow cytometry in human breast cancer MCF-7 cells in vitro. Galaxamide and its analogues effectively induced toxicity in human hepatocellular carcinoma HepG2, human breast carcinoma MCF-7, human epitheloid cervix carcinoma HeLa, and human breast carcinoma MB-MDA-231 cell lines. Amongst them, compound 3 exhibited excellent toxicity towards MCF-7 cells. This galaxamide analogue significantly induced apoptosis in a dose-dependent manner in MCF-7 cells involves cell cycle arrest in the G1 phase, a reduction of MMP, and a marked increase in generation of ROS. Particularly, compound 3 of galaxamide analogues might be a potential candidate for the treatment of breast cancer.

Design and Synthesis of Analogues of Marine Natural Product Galaxamide, an N-methylated Cyclic Pentapeptide, as Potential Anti-Tumor Agent in Vitro.

Herein, we report design and synthesis of novel 26 galaxamide analogues with N-methylated cyclo-pentapeptide, and their in vitro anti-tumor activity towards the panel of human tumor cell line, such as, A549, A549/DPP, HepG2 and SMMC-7721 using MTT assay. We have also investigated the effect of galaxamide and its representative analogues on growth, cell-cycle phases, and induction of apoptosis in SMMC-7721 cells in vitro. Reckon with the significance of conformational space and N-Me aminoacid (aa) comprising this compound template, we designed the analogues with modification in N-Me-aa position, change in aa configuration from l to d aa and substitute one Leu-aa to d/l Phe-aa residue with respective to the parent structure. The efficient solid phase parallel synthesis approach is employed for the linear pentapeptide residue containing N-Me aa, followed by solution phase macrocyclisation to afford target cyclo pentapeptide compounds. In the present study, all galaxamide analogues exhibited growth inhibition in A549, A549/DPP, SMMC-7721 and HepG2 cell lines. Compounds 6, 18, and 22 exhibited interesting activities towards all cell line tested, while Compounds 1, 4, 15, and 22 showed strong activity towards SMMC-7221 cell line in the range of 1-2 µg/mL IC50. Flow cytometry experiment revealed that galaxamide analogues namely Compounds 6, 18, and 22 induced concentration dependent SMMC-7721 cell apoptosis after 48 h. These compounds induced G0/G1 phase cell-cycle arrest and morphological changes indicating induction of apoptosis. Thus, findings of our study suggest that the galaxamide and its analogues 6, 18 and 22 exerted growth inhibitory effect on SMMC-7721 cells by arresting the cell cycle in the G0/G1 phase and inducing apoptosis. Compound 1 showed promising anti-tumor activity towards SMMC-7721 cancer cell line, which is 9 and 10 fold higher than galaxamide and reference DPP (cisplatin), respectively.

Oryzamides A-E, Cyclodepsipeptides from the Sponge-Derived Fungus Nigrospora oryzae PF18.

Three new cyclohexadepsipeptides, oryzamides A-C (1-3), two isolation artifacts, oryzamides D (4) and E (5), and the known congener scopularide A (6), all possessing a rare 3-hydroxy-4-methyldecanoic acid (HMDA) substructure, were isolated from the mycelial extract of the sponge-derived fungus Nigrospora oryzae PF18. Their planar structures were elucidated by spectroscopic analysis and comparison with the literature data. The absolute configurations were determined using the advanced Marfey's method and single-crystal X-ray diffraction analysis. Among them, oryzamides D (4) and E (5) were a pair of diastereomers at the sulfur atom of the l-methionine sulfoxide residue, which showcased the possible separation of a pair of methionine sulfoxide diastereomers. The X-ray crystal structure of scopularide A (6) was obtained for the first time, thereby establishing its relative and absolute configuration at C-4 of the HMDA residue. Oryzamides A-C (1-3) did not display cytotoxic, antibacterial, antiparasitic, and NF-κB inhibitory activities.

A new sesquiterpene from the gorgonian coral Menella sp.

A new sesquiterpene named menecubebane B (1) and a known analogue (2) were isolated from the gorgonian coral Menella sp. Their structures were elucidated by the extensive analyses of spectroscopic data and by the comparison with related literature. Cytotoxic effect against both Eca9706 and HeLa cell lines was evaluated, revealing 1 exhibited moderate cytotoxicity against the two cell lines involved with IC50 values being 20.8 and 30.6 µM, respectively.

9,11-Secosteroids with cytotoxic activity from the South China Sea gorgonian coral Subergorgia suberosa.

Nine new 9,11-secosterols (1-9), containing the same 3ß,6α,11-trihydroxy-9,11-seco-5α-cholest-7-en-9-one steroidal nucleus, whereas possessing an array of structurally diverse side chains, along with fourteen known 9,11-secosterol compounds (10-23), were isolated from the South China Sea gorgonian coral Subergorgia suberosa, of which 3/4, 5/6, 7/8, and the known compounds 11/12, 20/21 were five pairs of inseparable C-24 epimers. Their structures were established by the extensive analyses of 1D and 2D NMR spectra, high-resolution chemical ionization mass spectrometry (HRCIMS), and by the comparison with literature data. Cytotoxic effect of these metabolites against the growth of HeLa cell lines was evaluated. The result showed that the inhibitory effect of compounds 1-23 varied considerably depending on the nature of the side chain in spite of sharing the same steroidal nucleus. Compound 19, featuring both the absence of hydroxyl group and the presence of double bond in the stigmasterol side chain, exhibited the most potent cytotoxicity with IC50 being 15.1 µM. The preliminary structure activity relationship studies identified some important structural features considerably influencing the biological effect deserved, providing valuable information for chemists and pharmacologists to design and synthesize more effective antitumor agents bearing the 9,11-secosteroid framework.