Oxidation and reduction of sulfite contribute to susceptibility and detoxification of SO2 in Populus × canescens leaves

Key Message

The critical level for SO ₂ susceptibility of Populus × canescens is approximately 1.2 μL L ^?1 SO ₂ . Both sulfite oxidation and sulfite reduction and assimilation contribute to SO ₂ detoxification.

Abstract

In the present study, uptake, susceptibility and metabolism of SO₂ were analyzed in the deciduous tree species poplar (Populus × canescens). A particular focus was on the significance of sulfite oxidase (SO) for sulfite detoxification, as SO has been characterized as a safety valve for SO₂ detoxification in herbaceous plants. For this purpose, poplar plants were exposed to different levels of SO₂ (0.65, 0.8, 1.0, 1.2 μL L^?1) and were characterized by visible injuries and at the physiological level. Gas exchange parameters (stomatal conductance for water vapor, CO₂ assimilation, SO₂ uptake) of the shoots were compared with metabolite levels (sulfate, thiols) and enzyme activities [SO, adenosine 5′-phosphosulfate reductase (APR)] in expanding leaves (80–90 % expanded). The critical dosage of SO₂ that confers injury to the leaves was 1.2 μL L^?1 SO₂. The observed increase in sulfur containing compounds (sulfate and thiols) in the expanding leaves strongly correlated with total SO₂ uptake of the plant shoot, whereas SO₂ uptake rate was strongly correlated with stomatal conductance for water vapor. Furthermore, exposure to high concentration of SO₂ revealed channeling of sulfite through assimilatory sulfate reduction that contributes in addition to SO-mediated sulfite oxidation to sulfite detoxification in expanding leaves of this woody plant species.     

Cytotoxic metabolites from Perenniporia tephropora, an endophytic fungus from Taxus chinensis var. mairei

Based on bioactivity-oriented isolation, the EtOAc extract of a culture broth of the endophytic fungus Perenniporia tephropora Z41 from Taxus chinensis var. mairei, with strong anti-Pyricularia oryzae activity, afforded a new sesquiterpenoid, perenniporin A (1), together with three known compounds, ergosterol (2), rel-(+)-(2aR,5R,5aR,8S,8aS,8bR)-decahydro-2,2,5,8-tetramethyl-2H-naphtho[1,8-bc]genfuran-5-ol (3), and albicanol (4). Their structures were elucidated by means of spectroscopic methods. All the isolated compounds and the EtOAc extract of P. tephropora Z41 (EPT) were evaluated for their cytotoxic activity against three human cancer cell lines (HeLa, SMMC-7721, and PANC-1). EPT demonstrated significant cytotoxicity with IC₅₀ values ranging from 2 to 15 μg/mL. Compound 2 was the most cytotoxic constituent against the tested cell lines with IC₅₀ values of 1.16, 11.63, and 11.80 μg/mL, respectively, while compounds 1, 3, and 4 exhibited moderate cytotoxicity with IC₅₀ values ranging from 6 to 58 μg/mL. We conclude that the endophytic fungus P. tephropora is a promising source of novel and cytotoxic metabolites.     

Antimicrobial ergosteroids and pyrrole derivatives from halotolerant Aspergillus flocculosus PT05-1 cultured in a hypersaline medium

In order to obtain more structurally novel and bioactive lead compounds for subsequent drug discovery, we have shifted the focus of our study from traditional microbial resources to ‘extremophiles’. In this study, a halotolerant fungus Aspergillus flocculosus PT05-1 was isolated from the sediment of Putian saltern of Fujian Province of China in a hypersaline medium. Two new compounds, (22R,23S)-epoxy-3β,11α,14β,16β-tetrahydroxyergosta-5,7-dien-12-one (1) and 6-(1H-pyrrol-2-yl)hexa-1,3,5-trienyl-4-methoxy-2H-pyran-2-one (5) (existed as a pair of epimers with the configuration of 1E,3Z,5E and 1E,3E,5E separately), along with nine known compounds were isolated and identified from the fermentation broth of A. flocculosus PT05-1 grown at a 10 % saline medium. New ergosteroid 1 together with 7-nor-ergosterolide (2) and 3β-hydroxyergosta-8,24(28)-dien-7-one (3) showed cytotoxicity against HL-60 and BEL-7402 cells with IC₅₀ values of 12–18 μM, and antimicrobial activity against Enterobacter aerogenes, Pseudomonas aeruginosa, and Candida albicans with MIC values of 1.6–15 μM, respectively. New compound 5 exhibited antibacterial effect on E. aerogenes with MIC value of 3.7 μM. This study also showed great prospects in developing medicinal resources from extremophiles.     

Hyperfine interactions and electron distribution in FeIIFeI and FeIFeI models for the active site of the [FeFe] hydrogenases: Mössbauer spectroscopy studies of low-spin FeI

Mössbauer studies of [{μ-S(CH₂C(CH₃)₂CH₂S}(μ-CO)Fe^IIFe^I(PMe₃)₂(CO)₃]PF₆ (1 _OX ), a model complex for the oxidized state of the [FeFe] hydrogenases, and the parent Fe^IFe^I derivative are reported. The paramagnetic 1 _OX is part of a series featuring a dimethylpropanedithiolate bridge, introducing steric hindrance with profound impact on the electronic structure of the diiron complex. Well-resolved spectra of 1 _OX allow determination of the magnetic hyperfine couplings for the low-spin distal Fe^I ( $ {\text{Fe}}^{\text{I}} _{\text{ D}} $ Fe D I ) site, A _x,y,z  = [?24 (6), ?12 (2), 20 (2)] MHz, and the detection of significant internal fields (approximately 2.3 T) at the low-spin ferrous site, confirmed by density functional theory (DFT) calculations. Mössbauer spectra of 1 _OX show nonequivalent sites and no evidence of delocalization up to 200 K. Insight from the experimental hyperfine tensors of the Fe^I site is used in correlation with DFT to reveal the spatial distribution of metal orbitals. The Fe–Fe bond in [Fe₂{μ-S(CH₂C(CH₃)₂CH₂S}(PMe₃)₂(CO)₄] (1) involving two $ d_{{z^{2} }} $ d z 2 -type orbitals is crucial in keeping the structure intact in the presence of strain. On oxidation, the distal iron site is not restricted by the Fe–Fe bond, and thus the more stable isomer results from inversion of the square pyramid, rotating the $ d_{{z^{2} }} $ d z 2 orbital of $ {\text{Fe}}^{\text{I}} _{\text{ D}} $ Fe D I . DFT calculations imply that the Mössbauer properties can be traced to this $ d_{{z^{2} }} $ d z 2 orbital. The structure of the magnetic hyperfine coupling tensor, A, of the low-spin Fe^I in 1 _OX is discussed in the context of the known A tensors for the oxidized states of the [FeFe] hydrogenases.     

Cytotoxic metabolites from the cultures of endophytic fungi from Panax ginseng

Two strains of endophytic fungi, Penicillium melinii Yuan-25 and Penicillium janthinellum Yuan-27, with strong anti-Pyricularia oryzae activity, were obtained from the roots of Panax ginseng. Based on bioactivity-oriented isolation, a new benzaldehyde derivative, ginsenocin (1), together with six known compounds, methyl 2,4-dihydroxy-3,5,6-trimethylbenzoate (2), 3,4,5-trimethyl-1,2-benzenediol (3), penicillic acid (4), mannitol (5), ergosterol (6), and ergosterol peroxide (7), were separated from the EtOAc extract of Yuan-25 culture, while brefeldin A (8) was isolated as the major constituent from the EtOAc extract of Yuan-27 culture. The chemical structures were determined based on spectroscopic methods. All the isolated compounds 1–8 were evaluated for their cytotoxicity against six human cancer cell lines. Brefeldin A (8) was the most cytotoxic constituent against all the tested cell lines with IC₅₀ values <0.12 μg/ml, while ginsenocin (1) and penicillic acid (4) also exhibited potent cytotoxicity with IC₅₀ values ranging from 0.49 to 7.46 μg/ml. Our results suggest that endophytic fungi isolated from P. ginseng are a promising natural source of potential anticancer agents.     

2-Phenylpyridine ruthenacycles as effectors of glucose oxidase activity: inhibition by RuII and activation by RuIII

Cyclometalated Ru^II derivatives of 2-phenylpyridine (Hphpy) [Ru(phpy)(bpy)₂]Cl (1a) and [Ru(phpy)(phen)₂]Cl (1b) (bpy is 2,2′-bipyridine, phen is 1,10-phenanthroline) behave as noncompetitive inhibitors of glucose oxidase from Aspergillus niger in the enzyme-catalyzed oxidation of d-glucose by O₂ into the corresponding lactone at pH 5.0 and 25 °C. The enzymatic activity has been measured by monitoring the O₂ consumption. The inhibition constants K _i are 0.036 and 0.017 M for 1a and 1b, respectively, indicating that 1b inhibits the enzymatic activity more efficiently than 1a. The well-known coordination compound [Ru(bpy)₃]Cl₂ (2) behaves, in contrast, as a competitive inhibitor, with K _i = 0.018 M under the same conditions. The monophasic consumption of O₂ in the case of 1a, 1b, and 2 is replaced by a distinct two-phase kinetics in the presence of the cyclometalated Ru^III compound [Ru(phpy)(bpy)₂]Cl₂ (3), which was obtained from 1a in the presence of a large excess of H₂O₂ and the iron TAML activator. Interestingly, the rates of the first and the second phases are influenced by 3 in a different way. The rate of the first phase is noticeably higher in the presence of Ru^III, although the dependence is nonmonotonic and maximal acceleration is observed at the lowest loadings of 3. The rate of the second phase decreases monotonically on increasing the concentration of the ruthenium complex in solution. The nonmonotonic action of 3 was confirmed by using the doubly cyclometalated Ru^III derivative [Ru(phpy)₂(bpy)]Cl. The diverse rate variations induced by 3 accounted for acceleration by Ru^III of the O₂ reduction by the reduced form of glucose oxidase during the first phase, which ceases after the enzymatic reduction of Ru^III to the Ru^II species, the latter behaving similarly to 1a as the inhibitor of the enzyme.     

Bioactive compounds of <Emphasis Type="Italic">Aspergillus terreus</Emphasis>—F7, an endophytic fungus from <Emphasis Type="Italic">Hyptis suaveolens</Emphasis> (L.) Poit

The compounds terrein (1), butyrolactone I (2), and butyrolactone V (3) were isolated from the ethyl acetate extract (EtOAc) of the endophytic fungus Aspergillus terreus—F7 obtained from Hyptis suaveolens (L.) Poit. The extract and the compounds presented schistosomicidal activity against Schistosoma mansoni; at 100 µg/mL for EtOAc extract, 1297.3 µM for compound 1, 235.6 µM for compound 2, and 454.1 µM for compound 3, they killed 100% of the parasites after 72 h of treatment. Compounds 1, 2, and 3 exerted moderate leishmanicidal activity against Leishmania amazonensis (IC₅₀ ranged from 23.7 to 78.6 µM). At 235.6 and 227.0 µM, compounds 2 and 3, respectively, scavenged 95.92 and 95.12% of the DPPH radical (2,2-diphenyl-1-picryl-hydrazyl), respectively. Regarding the cytotoxicity against the breast tumor cell lines MDA-MB-231 and MCF-7, compound 2 gave IC₅₀ of 34.4 and 17.4 µM, respectively, while compound 3 afforded IC₅₀ of 22.2 and 31.9 µM, respectively. At 117.6 µM, compound 2 inhibited the growth of and killed the pathogen Escherichia coli (ATCC 25922). Compounds 1, 2, and 3 displayed low toxicity against the normal line of human lung fibroblasts (GM07492A cells), with IC₅₀ of 15.3?×?10³, 3.4?×?10³, and 5.8?×?10³ µM, respectively. This is the first report on (i) the in vitro schistosomicidal and leishmanicidal activities of the EtOAc extract of A. terreus—F7 and compounds 1, 2, and 3; and (ii) the antitumor activity of compounds 2 and 3 against MDA-MB-231 and MCF-7 cells.     

Endogenous nitric oxide generation in protoplast chloroplasts

Key message

NO generation is studied in the protoplast chloroplasts. NO, ONOO ^? and ROS (O ₂ ^? and H ₂ O ₂ ) are generated in chloroplasts. Nitric oxide synthase-like protein appears to be involved in NO generation.

Abstract

Nitric oxide stimulates chlorophyll biosynthesis and chloroplast differentiation. The present study was conducted to better understand the process of NO generation in the leaf chloroplasts and protoplasts. NO, peroxynitrite and superoxide anion were investigated in the protoplasts and isolated chloroplasts using specific dyes, confocal laser scanning and light microscopy. The level of NO was highest after protoplast isolation and subsequently decreased during culture. Suppression of NO signal in the presence of PTIO, suggests that diaminofluorescein-2 diacetate (DAF-2DA) detected NO. Detection of peroxynitrite, a reaction product of NO and superoxide anion, further suggests NO generation. Moreover, generation of NO and peroxynitrite in the chloroplasts of wild-type Arabidopsis and their absence or weak signals in the leaf-derived protoplasts of Atnoa1 mutants confirmed the reactivity of DAF-2DA and aminophenyl fluorescein to NO and peroxynitrite, respectively. Isolated chloroplasts also showed signal of NO. Suppression of NO signal in the presence of 100 μM nitric oxide synthase inhibitors [l-NNA, Nω-nitro-l-arginine and PBIT, S,S′-1,3-phenylene-bis(1,2-ethanediyl)-bis-isothiourea] revealed that nitric oxide synthase-like system is involved in NO synthesis. Suppression of NO signal in the protoplasts isolated in the presence of cycloheximide suggests de novo synthesis of NO generating protein during the process of protoplast isolation. Furthermore, the lack of inhibition of NO production by sodium tungstate (250 μM) and inhibition by l-NNA, and PBIT suggest involvement NOS-like protein, but not nitrate reductase, in NO generation in the leaf chloroplasts and protoplasts.     

Purple-leaved Ficus lyrata plants produced by overexpressing a grapevine VvMybA1 gene

Key message

This study established an efficient method of regenerating plants of Ficus lyrata and producing purple-leaved F. lyrata plants through genetic transformation using a VvMybA1 gene of grapevine.

Abstract

Ficus lyrata, a species with unique violin- or guitar-shaped leaves, was regenerated from leaf-derived calli cultured on Murashige and Skoog (MS) basal medium supplemented with 4.5 μM N-phenyl-N’-1, 2, 3-thiadiazol-5-yl urea (TDZ) and 0.5 μM α-naphthalene acetic acid (NAA). Leaf discs were inoculated with Agrobacterium tumefaciens strain EHA 105 harboring a binary vector DEAT that contains the VvMybA1 gene and neomycin phosphotransferase (npt II) gene and subsequently cultured on the established regeneration medium supplemented with 100 mg l^?1 kanamycin. Results showed that 87.5 % of the leaf discs produced kanamycin-resistant callus, and 68.8 % of them produced adventitious shoots. Transgenic plants with three leaf colors including green, green-purple, and purple were produced. Regular and quantitative real-time PCR analyses confirmed the integration of transgenes into the host genome. Semi-quantitative RT-PCR analysis indicated that the VvMybA1 gene was responsible for the purple-colored phenotype. Purple-leaved plants with strong color stability grew vigorously in a greenhouse. This study illustrated the feasibility of using a genetically engineered VvMybA1 gene for drastic modification of leaf color of an important woody ornamental plant.     

Di- and polynuclear silver(I) saccharinate complexes of tertiary diphosphane ligands: synthesis, structures, in vitro DNA binding, and antibacterial and anticancer properties

A series of new silver(I) saccharinate (sac) complexes, [Ag₂(sac)₂(μ-dppm)H₂O]·H₂O (1), {[Ag₂(μ-sac)₂(μ-dppe)]·3H₂O·CH₂Cl₂} _n (2), [Ag₂(μ-sac)₂(μ-dppp)] _n (3), and [Ag(sac)(μ-dppb)] _n (4) [dppm is 1,1-bis(diphenylphosphino)methane, dppe is 1,2-bis(diphenylphosphino)ethane, dppp is 1,3-bis(diphenylphosphino)propane, and dppb is 1,4-bis(diphenylphosphino)butane], have been synthesized and characterized by C, H, N elemental analysis, IR spectroscopy, ¹H NMR, ¹³C NMR, and ³¹P NMR spectroscopy, electrospray ionization mass spectrometry, and thermogravimetry–differential thermal analysis. Single-crystal X-ray studies show that the diphosphanes act as bridging ligands to yield a dinuclear complex (1) and one-dimensional coordination polymers (2 and 4), whereas the sac ligand adopts a μ₂-N/O bridging mode in 2, and is N-coordinated in 1 and 4. The interaction of the silver(I) complexes with fish sperm DNA was investigated using UV–vis spectroscopy, fluorescence spectroscopy, and agarose gel electrophoresis. The binding studies indicate that the silver(I) complexes can interact with fish sperm DNA through intercalation, and complexes 1 and 3 have the highest binding affinity. The gel electrophoresis assay further confirms the binding of the complexes with the pBR322 plasmid DNA. The minimum inhibitory concentrations of the complexes indicate that complex 1 exhibits very high antibacterial activity against standard bacterial strains of Escherichia coli, Salmonella typhimurium, and Staphylococcus aureus, being much higher than those of AgNO₃, silver sulfadiazine, ciprofloxacin, and gentamicin. Moreover, complexes 1–3 exhibit very high cytotoxic activity against A549 and MCF-7 cancer cell lines, compared with AgNO₃ and cisplatin. The bacterial and cell growth inhibitions of the silver(I) complexes are closely related to their DNA binding affinities.     

Cytotoxic effect and molecular docking of 4-ethoxycarbonylmethyl-1-(piperidin-4-ylcarbonyl)-thiosemicarbazide—a novel topoisomerase II inhibitor

The preliminary cytotoxic effect of 4-ethoxycarbonylmethyl-1-(piperidin-4-ylcarbonyl)-thiosemicarbazide hydrochloride (1)—a potent topoisomerase II inhibitor—was measured using a MTT assay. It was found that the compound decreased the number of viable cells in both estrogen receptor-positive MCF-7 and estrogen receptor-negative MDA-MB-231breast cancer cells, with IC₅₀ values of 146?±?2 and 132?±?2 μM, respectively. To clarify the molecular basis of the inhibitory action of 1, molecular docking studies were carried out. The results suggest that 1 targets the ATP binding pocket.

Pseudomonas hunanensis sp. nov., Isolated from Soil Subjected to Long-Term Manganese Pollution

A Gram-negative, polar flagella, rod-shaped bacterium LV ^T was isolated from a soil sample subjected to long-term manganese pollution in Hunan Province, China. Cells grow optimally on Luria–Bertani agar medium at 30 °C in the presence of 0–5.0 % (w/v) NaCl and pH 7–8. 16S rRNA gene sequence analysis revealed that strain LV ^T belonged to the genus Pseudomonas, with sequence similarity values of 98.6, 98.2, 98.7, and 97.3 % to Pseudomonas monteilii BCRC 17520 ^T , Pseudomonas putida BCRC 10459 ^T , Pseudomonas plecoglossicida BCRC 17517 ^T , and Pseudomonas asplenii BCRC 17131 ^T , respectively. The level of DNA–DNA relatedness between the five strains was <30 %. The DNA G+C content of strain LV ^T is 68.8 mol%. Chemotaxonomic data revealed that the strain LV^T possesses ubiquinone Q-9. The polar lipid profile of strain LV ^T contained diphosphatidylglycerol, phosphatidylglycerol, phosphatidylcholine, and phosphatidylethanolamine. The major cellular fatty acids present are C_10:03-OH (12.33 %), C_16:0 (23.99 %), summed feature 3(C_16:1ω7c and/or C_16:1ω6c), and summed feature 8(C_{18:1 ω7c} and C_{18:1 ω6c}). Based on the genotypic, chemotaxonomic and phenotypic data, strain LV ^T is distinguishable from related members of the genus Pseudomonas. Thus, strain LV ^T represents a novel species of the genus Pseudomonas, for which the name Pseudomonas hunanensis sp. nov. is proposed. The type strain is LV ^T (=CICC 10558^T = NCCB 100446^T).     

Three new sterigmatocystin analogues from marine-derived fungus Aspergillus versicolor MF359

During the systematic screening of active compounds from marine-derived fungi, the extract of a strain of Aspergillus versicolor MF359 isolated from a marine sponge of Hymeniacidon perleve was identified for detailed chemical investigation. Three new secondary metabolites, named hemiacetal sterigmatocystin (1), acyl-hemiacetal sterigmatocystin (2), and 5-methoxydihydrosterigmatocystin (3), together with a known compound, aversin (4), were characterized. 1 represents a first structure of sterigmatocystin hemiacetal from nature. The antibacterial activities of these identified compounds were evaluated against Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, Bacillus subtilis, and Pseudomonas aeruginosa. Compound 3 showed activity against S. aureus and B. subtilis with MIC values of 12.5 and 3.125 μg/mL, respectively.     

Transformation of the naturally occurring frog skin peptide, alyteserin-2a into a potent, non-toxic anti-cancer agent

Alyteserin-2a (ILGKLLSTAAGLLSNL.NH₂) is a cationic, amphipathic α-helical cell-penetrating peptide, first isolated from skin secretions of the midwife toad Alytes obstetricans. Structure–activity relationships were investigated by synthesizing analogs of alyteserin-2a in which amino acids on the hydrophobic face of the helix were replaced by l-tryptophan and amino acids on the hydrophilic face were replaced by one or more l-lysine or d-lysine residues. The Trp-containing peptides display increased cytotoxic activity against non-small cell lung adenocarcinoma A549 cells (up to 11-fold), but hemolytic activity against human erythrocytes increases in parallel. The potency of the N15K analog against A549 cells (LC₅₀ = 13 μM) increases sixfold relative to alyteserin-2a and the therapeutic index (ratio of LC₅₀ for erythrocytes and tumor cells) increases twofold. Incorporation of a d-Lys¹¹ residue into the N15K analog generates a peptide that retains potency against A549 cells (LC₅₀ = 15 μM) but whose therapeutic index is 13-fold elevated relative to the native peptide. [G11k, N15K] alyteserin-2a is also active against human hepatocarcinoma HepG2 cells (LC₅₀ = 26 μM), breast adenocarcinoma MDA-MB-231 cells (LC₅₀ = 20 μM), and colorectal adenocarcinoma HT-29 cells (LC₅₀ = 28 μM). [G11k, N15K] alyteserin-2a, in concentrations as low as 1 μg/mL, significantly (P < 0.05) inhibits the release of the immune-suppressive cytokines IL-10 and TGF-β from unstimulated and concanavalin A-stimulated peripheral blood mononuclear cells. The data suggest a strategy of increasing the cationicity while reducing the helicity of naturally occurring amphipathic α-helical peptides to generate analogs with improved cytotoxicity against tumor cells but decreased activity against non-neoplastic cells.     

Nickel/zinc-catalyzed decarbonylative addition of anhydrides to alkynes: A DFT study

Density functional theory (DFT) was used to investigate the nickel- or nickel(0)/zinc- catalyzed decarbonylative addition of phthalic anhydrides to alkynes. All intermediates and transition states were optimized completely at the B3LYP/6-31+G(d,p) level. Calculated results indicated that the decarbonylative addition of phthalic anhydrides to alkynes was exergonic, and the total free energy released was ?87.6 kJ mol^?1. In the five-coordinated complexes M4a and M4b, the insertion reaction of alkynes into the Ni-C bond occurred prior to that into the Ni-O bond. The nickel(0)/zinc-catalyzed decarbonylative addition was much more dominant than the nickel-catalyzed one in whole catalytic decarbonylative addition. The reaction channel CA→M1'→T1'→M2'→T2'→M3a'→M4a'→T3a1'→M5a1' →T4a1'→M6a'→P was the most favorable among all reaction pathways of the nickel- or nickel(0)/zinc- catalyzed decarbonylative addition of phthalic anhydrides to alkynes. And the alkyne insertion reaction was the rate-determining step for this channel. The additive ZnCl₂ had a significant effect, and it might change greatly the electron and geometry structures of those intermediates and transition states. On the whole, the solvent effect decreased the free energy barriers.

Biological evaluation of a cytotoxic 2-substituted benzimidazole copper(II) complex: DNA damage,antiproliferation and apoptotic induction activity in human cervical cancer cells

Exploring novel chemotherapeutic agents is a great challenge in cancer medicine. To that end, 2-substituted benzimidazole copper(II) complex, [Cu(BMA)Cl₂]·(CH₃OH) (1) [BMA = N,N′-bis(benzimidazol-2-yl-methyl)amine], was synthesized and its cytotoxicity was characterized. The interaction between complex 1 and calf thymus DNA was detected by spectroscopy methods. The binding constant (K _b = 1.24 × 10⁴ M^?1) and the apparent binding constant (K _app = 6.67 × 10⁶ M^?1) of 1 indicated its moderate DNA affinity. Complex 1 induced single strand breaks of pUC19 plasmid DNA in the presence of H₂O₂ through an oxidative pathway. Cytotoxicity studies proved that complex 1 could inhibit the proliferation of human cervical carcinoma cell line HeLa in both time- and dose-dependent manners. The results of nuclei staining by Hoechst 33342 and alkaline single-cell gel electrophoresis proved that complex 1 caused cellular DNA damage in HeLa cells. Furthermore, treatment of HeLa cells with 1 resulted in S-phase arrest, loss of mitochondrial potential, and up-regulation of caspase-3 and -9 in HeLa cells, suggesting that complex 1 was capable of inducing apoptosis in cancer cells through the intrinsic mitochondrial pathway.     

Three antimycobacterial metabolites identified from a marine-derived Streptomyces sp. MS100061

In the course of a screening program for bioactive compounds from a marine natural product library, a newly isolated Actinomycetes strain, designated as MS100061, exhibited strong anti-Mycobacterium bovis Bacillus Calmette–Guérin (BCG) activity. The strain belongs to the genus Streptomyces according to its morphological and 16S rDNA phylogenetic analysis. Bioassay-guided isolation resulted in a new spirotetronate, lobophorin G (1), together with two known compounds, lobophorins A (2) and B (3). The structures were elucidated by extensive spectroscopic methods and comparison with literatures. Compounds 1–3 were subjected to anti-BCG, antituberculosis, and antibacterial screening and exhibited potent anti-BCG activity with minimum inhibitory concentration (MIC) values of 1.56, 1.56, and 0.78 μg/ml, respectively, and moderate anti-Mycobacterium tuberculosis H37Rv activity with MIC values of 32, 32, and 16 μg/ml, respectively. The MIC values of compounds 1–3 against Bacillus subtilis were 3.125, 12.5, and 1.56 μg/ml, respectively, indicating great potential for antibacterial drugs. In addition, this is the first report of the anti-BCG and antituberculosis activities of lobophorins.     

Dioxovanadium(V) and μ-oxo bis[oxovanadium(V)] complexes containing thiosemicarbazone based ONS donor set and their antiamoebic activity

Neutral dioxovanadium (V) complexes [VO₂(HL)] (H₂L = I: 1, H₂L = II: 2 and H₂L = III: 3; H₂L are the thiosemicarbazones H₂pydx-tsc (I), H₂pydx-chtsc (II) and H₂pydx-clbtsc (III); pydx = pyridoxal, tsc = thiosemicarbazide, chtsc = N₄-cyclohexylthiosemicarbazide, clbtsc = N₄-(2-chloro)benzylthiosemicarbazide) have been isolated and characterised on the basis of elemental and electrochemical analyses, spectroscopic (IR, UV-Vis, ¹H and ⁵¹V NMR) data, thermogravimetric studies and reactivity patterns. These complexes are stable in solution at ambient temperature but heating of the methanolic solutions yields the μ-oxo binuclear complexes [(VOL)₂μ-O] (H₂L = I: 4, H₂L = II: 5, H₂L = III: 6). Treatments of dioxo species with H₂O₂ yield oxoperoxo species, the formations of which have been established spectrophotometrically. Similarly, the formations of oxohydroxo species, an intermediate proposed during the catalytic action of haloperoxidases, have also been established in solution by treating 1, 2 and 3 with a methanolic solution of HCl. The antiamoebic activities were carried out to ascertain the effectiveness of dioxovanadium(V) and μ-oxobis(oxovanadium(V)) complexes in comparison to their corresponding thiosemicarbazones. These complexes possess noteworthy potencies against HM1:1MSS strain of Entamoeba histolytica. Complexes 2, 3, 5 and 6 showed less IC₅₀ values than metronidazole, indicating that these metal thiosemicarbazones may be the lead molecules to inhibit the growth of E. histolytica. Within the series, complex 5 showed the most promising amoebicidal activity (IC₅₀ = 0.5 μM versus IC₅₀ = 1.8 of metronidazole).     

Biotransformation of Methylphenylacetonitriles by Brazilian Marine Fungal Strain Aspergillus sydowii CBMAI 934: Eco-friendly Reactions

This study reports the biotransformation of methylphenylacetonitriles by Brazilian marine filamentous fungus Aspergillus sydowii CBMAI 934 under eco-friendly reaction conditions. The phenylacetonitrile 1, 2-methylphenylacetonitrile 2, 3-methylphenylacetonitrile 3, and 4-methylphenylacetonitrile 4 were quantitatively biotransformed into 2-hydroxyphenylacetic 1a, 2-methylphenylacetic acid 2a, 3-methylphenylacetic acid 3a, and 4-methylphenylacetic acid 4a by enzymatic processes using whole cell as biocatalyst. The marine fungus A. sydowii CBMAI 934 is thus a promising biocatalyst for the preparation of important carboxylic acids under mild conditions (pH 7.5 and 32 °C) from nitrile compounds.