Nitrification is the rate limiting step in the nitrogen removal processes since nitrifiers have high oxygen demand, but poorly compete with aerobic heterotrophs. In a laboratory-scaled system, we ...investigated a process of ammonium oxidation under ferric-iron reducing condition (feammox) in the presence of organic carbon using influents with high NH
and COD contents, and ferrihydrite as the only electron acceptor. Batch incubations testing influents with different NH
and COD concentrations revealed that the COD/NH
ratio of 1.4 and the influent redox potential ranging from - 20 to + 20 mV led to the highest removal efficiencies, i.e. 98.3% for NH
and 58.8% for COD. N
was detected as the only product of NH
conversion, whereas NO
and NO
were not detected. While operating continuously with influent having a COD/NH
ratio of 1.4, the system efficiently removed NH
(> 91%) and COD (> 54%) within 6 day retention time. Fluorescence in situ hybridization analyses using Cy3-labeled 16S rRNA oligonucleotide probes revealed that gamma-proteobacteria dominated in the microbial community attaching to the matrix bed of the system. The iron-reduction dependent NH
and COD co-removal with a thorough conversion of NH
to N
demonstrated in this study would be a novel approach for nitrogen treatment.
In our search for novel histone deacetylases inhibitors, we have designed and synthesized a series of novel hydroxamic acids and N‐hydroxybenzamides incorporating quinazoline heterocycles (4a – 4i, ...6a – 6i). Bioevaluation showed that these quinazoline‐based hydroxamic acids and N‐hydroxybenzamides were potently cytotoxic against three human cancer cell lines (SW620, colon; PC‐3, prostate; NCI‐H23, lung). In term of cytotoxicity, several compounds, e.g., 4g, 4c, 4g – 4i, 6c, and 6h, displayed from 5‐ up to 10‐fold higher potency than SAHA (suberoylanilidehydroxamic acid, vorinostat). The compounds were also generally comparable to SAHA in inhibiting HDACs with IC50 values in sub‐micromolar range. Some compounds, e.g., 4g, 6c, 6e, and 6h, were even more potent HDAC inhibitors compared to SAHA in HeLa extract assay. Docking studies demonstrated that the compounds tightly bound to HDAC2 at the active binding site with binding affinities higher than that of SAHA. Detailed investigation on the estimation of absorption, distribution, metabolism, excretion, and toxicity (ADMET) suggested that compounds 4g, 6c, and 6g, while showing potent HDAC2 inhibitory activity and cytotoxicity, also potentially displayed ADMET characteristics desirable to be expected as promising anticancer drug candidates.
Herein, we report the design, synthesis and evaluation of novel (E)‐3‐(3‐oxo‐4‐substituted‐3,4‐dihydro‐2H‐benzob1,4oxazin‐6‐yl)‐N‐hydroxypropenamides (4 a–i, 7 a–g) targeting histone deacetylases. ...Three human cancer cell lines were used to test the cytotoxicity of the synthesized compounds (SW620, colon; PC‐3, prostate; NCI−H23, lung cancer); inhibitory activity towards HDAC; anticancer activity; as well as their impact on the cell cycle and apoptosis. As a result, compounds 4 a–i bearing the alkyl substituents seemed to be less potent than the benzyl‐containing compounds 7 a–g in all biological assays. Compounds 7 e–f were found to be the most active HDAC inhibitors with IC50 of 1.498±0.020 μM and 1.794±0.159 μM, respectively. In terms of cytotoxicity and anticancer assay, 7 e and 7 f also showed good activity with IC50 values in the micromolar range. In addition, the cell cycle and apoptosis of SW620 were affected by compound 7 f in almost a similar manner to that of reference compound SAHA. Docking assays were carried out for analysis the binding mode and selectivity of this compound toward 8 HDAC isoforms. Overall, our data confirmed that the inhibition of HDAC plays a pivotal role in their anticancer activity.
In our search for new small molecules activating procaspase‐3, we have designed and synthesized a series of new acetohydrazides incorporating both 2‐oxoindoline and 4‐oxoquinazoline scaffolds. ...Biological evaluation showed that a number of these acetohydrazides were comparably or even more cytotoxic against three human cancer cell lines (SW620, colon cancer; PC‐3, prostate cancer; NCI−H23, lung cancer) in comparison to PAC‐1, a first procaspase‐3 activating compound, which was used as a positive control. One of those new compounds, 2‐(6‐chloro‐4‐oxoquinazolin‐3(4H)‐yl)‐N′‐(3Z)‐5‐methyl‐2‐oxo‐1,2‐dihydro‐3H‐indol‐3‐ylideneacetohydrazide activated the caspase‐3 activity in U937 human lymphoma cells by 5‐fold higher than the untreated control. Three of the new compounds significantly induced necrosis and apoptosis in U937 cells.
The present article describes the synthesis and biological activity of various series of novel hydroxamic acids incorporating quinazolin‐4(3H)‐ones as novel small molecules targeting histone ...deacetylases. Biological evaluation showed that these hydroxamic acids were potently cytotoxic against three human cancer cell lines (SW620, colon; PC‐3, prostate; NCI−H23, lung). Most compounds displayed superior cytotoxicity than SAHA (suberoylanilide hydroxamic acid, Vorinostat) in term of cytotoxicity. Especially, N‐hydroxy‐7‐(7‐methyl‐4‐oxoquinazolin‐3(4H)‐yl)heptanamide (5b) and N‐hydroxy‐7‐(6‐methyl‐4‐oxoquinazolin‐3(4H)‐yl)heptanamide (5c) (IC50 values, 0.10–0.16 μm) were found to be approximately 30‐fold more cytotoxic than SAHA (IC50 values of 3.29–3.67 μm). N‐Hydroxy‐7‐(4‐oxoquinazolin‐3(4H)‐yl)heptanamide (5a; IC50 values of 0.21–0.38 μm) was approximately 10‐ to 15‐fold more potent than SAHA in cytotoxicity assay. These compounds also showed comparable HDAC inhibition potency with IC50 values in sub‐micromolar ranges. Molecular docking experiments indicated that most compounds, as represented by 5b and 5c, strictly bound to HDAC2 at the active binding site with binding affinities much higher than that of SAHA.
In a bioelectrochemical system (BES) operated with a bioanode, the anode performance plays an important part in the overall performance. Fundamental aspects of bioanodes have been intensively ...investigated, enabling us to better understand the growth, kinetics functioning and interactions of anodophilic microorganisms. Recently, various technological advances have improved the properties and operation of anodes and have increased bioanode performance by up to tenfold. To further boost the performance of bioanodes by several orders of magnitude, practical microbiological approaches deserve more investigation. This article reviews the factors affecting bioanode performance, the recent advances and the prospective strategies for improving it. Future application perspectives of bioanodes are also proposed.
Microbial fuel cells (MFCs) that remove carbon as well as nitrogen compounds out of wastewater are of special interest for practice. We developed a MFC in which microorganisms in the cathode ...performed a complete denitrification by using electrons supplied by microorganisms oxidizing acetate in the anode. The MFC with a cation exchange membrane was designed as a tubular reactor with an internal cathode and was able to remove up to 0.146 kg NO3 --N m-3 net cathodic compartment (NCC) d-1 (0.080 kg NO3 --N m-3 total cathodic compartment d-1 (TCC)) at a current of 58 A m-3 NCC (32 A m-3 TCC) and a cell voltage of 0.075 V. The highest power output in the denitrification system was 8 W m-3 NCC (4 W m-3 TCC) with a cell voltage of 0.214 V and a current of 35 A m-3 NCC. The denitrification rate and the power production was limited by the cathodic microorganisms, which only denitrified significantly at a cathodic electrode potential below 0 V versus standard hydrogen electrode (SHE). This is, to our knowledge, the first study in which a MFC has both a biological anode and cathode performing simultaneous removal of an organic substrate, power production, and complete denitrification without relying on H2-formation or external added power.
Clerodendrum cyrtophyllum Turcz has been used in traditional medicine for the treatment of various diseases. In spite of its therapeutic applications, research on its toxicity and teratogenicity is ...still limited.
The study aimed to investigate the developmental toxicity of the ethanol extract of C. cyrtophyllum (EE) in zebrafish embryo model.
Major compounds from crude ethanol extract of Clerodendron cyrtophyllum Turcz leaves were determined using HPLC-DAD-Orbitrap-MS analysis. The developmental toxicity of EE were investigated using zebrafish embryo model. Zebrafish embryos at 6 h post-fertilization (hpf) were treated with EE at different concentrations. Egg coagulation, mortality, hatching, yolk sac edema, pericardial edema and teratogenicity were recorded each day for during a 5-day exposure. At time point 120 hpf, body length, pericardial area, heartbeat and yolk sac area were assessed. In order to elucidate molecular mechanisms for the developmental toxicity of EE, we further evaluated the effects of the EE on the expression of genes involved on signaling pathways affecting fish embryo’s development such as heart development (gata5, myl7, myh6, has2, hand2, nkx 2.5), oxidative stress (cat, sod1, gpx4, gstp2), wnt pathway (β-catenin, wnt3a, wnt5, wnt8a, wnt11), or cell apoptosis (p53, bax, bcl2, casp3, casp8, casp9, apaf-1, gadd45bb) using qRT-PCR analysis.
Our results demonstrated that three major components including acteoside, cirsilineol and cirsilineol-4'-O-β-D-glucopyranoside were identified from EE. EE exposure during 6–96 h post-fertilization (hpf) at doses ranging from 80 to 200 μg/mL increased embryo mortality and reduced hatching rate. EE exposure at 20 and 40 μg/mL until 72–120 hpf induced a series of malformations, including yolk sac edema, pericardial edema, spine deformation, shorter body length. Based on two prediction models using a teratogenic index (TI), a 25% lethality concentration (LD25) and the no observed-adverse-effect level (NOAEL), EE is considered as teratogenic for zebrafish embryos with TI (LC50/EC50) and LD25/NOAEC values at 96 hpf reaching 3.87 and 15.73 respectively. The mRNA expression levels of p53, casp8, bax/bcl2, gstp2, nkx2.5, wnt3a, wnt11, gadd45bb and gata5 were significantly upregulated by EE exposure at 20 and 40 μg/mL while the expression of wnt5, hand2 and bcl2 were downregulated.
These results provide evidence for toxicity effects of EE to embryo stages and provide an insight into the potential toxicity mechanisms on embryonic development.
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•Three novel series of indirubin-based hydroxamic acids were synthesized.•All three series exhibited potent HDAC inhibition.•All three series exhibited very strong cytotoxicity in ...three human cancer cell lines (SW620, PC-3, NCI-H23).•Representative compounds 4a and 7a arrested SW620 cells at G0/G1 phase.•Representative compounds 7a and 10a strongly induced apoptosis in SW620 cells.
Several novel indirubin-based N-hydroxybenzamides, N-hydropropenamides and N-hydroxyheptanamides (4a-h, 7a-h, 10a-h) were designed using a fragment-based approach with structural features extracted from several previously reported HDAC inhibitors, such as SAHA (vorinostat), MGCD0103 (mocetinostat), nexturastat A and PXD-101 (belinostat). The biological results reveal that our compounds showed excellent cytotoxicity toward three common human cancer cell lines (SW620, PC-3 and NCI-H23) with IC50 values ranging from 0.09 to 0.007 µM. The cytotoxicity of the compounds was equipotent or even up to 10-times more potent than adriamycin and up to 205-times more potent than SAHA. Among the series of N-hydroxypropenamides, compounds 10a-d were the most potent HDAC inhibitors as well as cytotoxicity toward the cell lines tested. In addition, the strong inhibitory activites toward HDAC of our compounds were observed with IC50 values of below-micromolar range. Especially, compound 4a inhibited HDAC6 with an IC50 value of 29-fold lower than that against HDAC2 isoform. Representative compounds 4a and 7a were found to significantly arrest SW620 cells at G0/G1 phase. Compounds 7a and 10a were found to strongly induce apoptosis in SW620 cells. Docking studies revealed some important features affecting the selectivity against HDAC6 isoform. The results clearly demonstrate the potential of the indirubin-hydroxamic acid hybrids and these compounds should be very promising for further development.
In our continuing search for novel small‐molecule anticancer agents, we designed and synthesized a series of novel (E)‐N'‐(3‐allyl‐2‐hydroxy)benzylidene‐2‐(4‐oxoquinazolin‐3(4H)‐yl)acetohydrazides ...(5), focusing on the modification of substitution in the quinazolin‐4(3H)‐one moiety. The biological evaluation showed that all 13 designed and synthesized compounds displayed significant cytotoxicity against three human cancer cell lines (SW620, colon cancer; PC‐3, prostate cancer; NCI‐H23, lung cancer). The most potent compound 5l displayed cytotoxicity up to 213‐fold more potent than 5‐fluorouracil and 87‐fold more potent than PAC‐1, the first procaspase‐activating compound. Structure–activity relationship analysis revealed that substitution of either electron‐withdrawing or electron‐releasing groups at positions 6 or 7 on the quinazolin‐4(3H)‐4‐one moiety increased the cytotoxicity of the compounds, but substitution at position 6 seemed to be more favorable. In the caspase activation assay, compound 5l was found to activate the caspase activity by 291% in comparison to PAC‐1, which was used as a control. Further docking simulation also revealed that this compound may be a potent allosteric inhibitor of procaspase‐3 through chelation of the inhibitory zinc ion. Physicochemical and ADMET calculations for 5l provided useful information of its suitable absorption profile and some toxicological effects that need further optimization to be developed as a promising anticancer agent.
Novel (E)‐Nʹ‐(3‐allyl‐2‐hydroxy)benzylidene‐2‐(4‐oxoquinazolin‐3(4H)‐yl)acetohydrazides with significant cytotoxicity against three human cancer cell lines were designed and synthesized. Compound 5l displayed cytotoxicity up to 213‐fold more potent than 5‐fluorouracil and 87‐fold‐more potent than PAC‐1, and activated caspase activity by 291% in comparison to that of PAC‐1.
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