The Bornean liverwort Gottschelia schizopleura was investigated phytochemically for the first time. Two new and four previously known clerodane-type diterpenoids were isolated from the MeOH extract of G. schizopleura through a series of chromatographic techniques. The structures of the new metabolites were established by analyses of their spectroscopic data (1D NMR, 2D NMR, HRESIMS and IR). All the isolated compounds 1-6 were tested against human promyelocytic leukaemia (HL-60), human colon adenocarcinoma (HT-29) and Mus musculus skin melanoma (B16-F10). Compound 1 and 2 showed active inhibition against HL-60 and B16-F10 cells.
One new compound, 12-epi-9-deacetoxyxenicin (1) along with a hydroperoxide product, 12-epi-9-deacetoxy-8-hydroperoxyxenicin (2) and two known sesquiterpenoids (3-4) were isolated from a population of Bornean soft coral Xenia sp. The structures of these secondary metabolites were elucidated based on their spectroscopic data. Compounds 1 and 2 showed cytotoxic activity against ATL cell line, S1T. In addition, compound 3 exhibited hyphal inhibition of Lagenidium thermophilum.
Two new halogenated nonterpenoids C15-acetogenins, nangallenes A-B (1-2), together with two known halogenated compounds itomanallene A (3) and 2,10-dibromo-3-chloro-α-chamigrene (4), were isolated and identified from the organic extract of the marine red alga Laurencia nangii Masuda collected from the coastal waters in Semporna, Borneo. Their structures were established by means of spectroscopic analysis including IR, high-resolution electrospray ionization mass spectrometry (HRESI-MS), and 1D and 2D NMR techniques. All these metabolites were submitted for the antifungal assay against four species of selected marine fungi. Compounds 1-4 showed potent activity against Haliphthoros sabahensis and Lagenidium thermophilum.
Four new bicyclogermacrenes, capgermacrenes D (1) E (2) F (3) and G (4) were isolated from a population of Bornean soft coral Capnella imbricata. The structures of these metabolites were elucidated based on their nuclear magnetic resonance and high-resolution electrospray ionisation mass spectrometry spectral data. These compounds showed bacteriastatic and bacteriacidal activities against Staphylococcus aureus and methicillin-resistant Staphylococcus aureus.
Soft corals are known to be prolific producers of a wide spectrum of biologically active cembranoids. One new cembranoid, sinularolide F (2), along with three known compounds, cembranolide (1), (E,E,E)-6,10,14-trimethyl-3-methylene-cis-3α,4,5,8,9,12,13,15α-octahydrocyclo tetradeca[β]furan-2(3H)-one (3), and denticulatolide (4), were isolated from the Bornean soft coral Sinularia sp. Compounds 2 and 4 showed potential anti-inflammatory activities against lipopolysaccharide-stimulated RAW 264.7 with IC50 values less than 6.25 µg/mL and anticancer activity against HL60 cell lines. The compounds' mechanisms of action were investigated via the Western blot evaluation of their protein markers. These activities could be attributed to the presence of tertiary methyl at C-8 and the compounds' 3D configurations.
A total of three carbazole alkaloids and essential oil from the leaves of Murraya koenigii (Rutaceae) were obtained and examined for their effects on the growth of five antibiotic resistant pathogenic bacteria and three tumor cell lines (MCF-7, P 388 and Hela). The structures of these carbazoles were elucidated based on spectroscopy data and compared with literature data, hence, were identified as mahanine (1), mahanimbicine (2) and mahanimbine (3). The chemical constituents of the essential oil were identified using Gas Chromatography-Mass Spectroscopy (GCMS). These compounds exhibited potent inhibition against antibiotic resistant bacteria such as Staphylococcus aureus (210P JTU), Psedomonas aeruginosa (ATCC 25619), Klebsiella pneumonia (SR1-TU), Escherchia coli (NI23 JTU) and Streptococcus pneumoniae (SR16677-PRSP) with significant minimum inhibition concentration (MIC) values (25.0-175.0 mg/mL) and minimum bacteriacidal concentrations (MBC) (100.0-500.0 mg/mL). The isolated compounds showed significant antitumor activity against MCF-7, Hela and P388 cell lines. Mahanimbine (3) and essential oil in particular showed potent antibacteria and cytotoxic effect with dose dependent trends (≤5.0 μg/mL). The findings from this investigation are the first report of carbazole alkaloids' potential against antibiotic resistant clinical bacteria, MCF-7 and P388 cell lines.
Many new isomeric dipyridothiazine dimers have been presented as molecules with anticancer potential. These compounds were obtained in efficient syntheses of 1,6-, 1,8-, 2,7- and 3,6-diazaphenothiazines with selected alkylaromatic linkers. The structures of these compounds has been proven with two-dimensional spectroscopic techniques (COSY, NOESY, HSQC and HMBC) and high-resolution mass spectrometry (HRMS). In silico analyses of probable molecular targets were performed using the Way2Drug server. All new dimers were tested for anticancer activity against breast cancer line MCF7 and colon cancer line SW480. Cytotoxicity was assessed on normal L6 muscle cells. The tested dimers had high anticancer potential expressed as IC50 and the selectivity index SI. The most active derivative, 4c, showed an IC50 activity of less than 1 µM and an SI selectivity index higher than 100. Moreover, the compounds were characterized by low toxicity towards normal cells, simultaneously indicating a high cytostatic potential.
Renewable solar energy is the key target to reduce fossil fuel consumption, minimize global warming issues, and indirectly minimizes erratic weather patterns. Herein, the authors synthesized an ultrathin reduced graphene oxide (rGO) nanosheet with ~47 nm via an improved Hummer's method. The TiO2 was deposited by RF sputtering onto an rGO nanosheet with a variation of temperature to enhance the photogenerated electron or charge carrier mobility transport for the photoanode component. The morphology, topologies, element composition, crystallinity as well as dye-sensitized solar cells' (DSSCs) performance were determined accordingly. Based on the results, FTIR spectra revealed presence of Ti-O-C bonds in every rGO-TiO2 nanocomposite samples at 800 cm-1. Besides, XRD revealed that a broad peak of anatase TiO2 was detected at ~25.4° after incorporation with the rGO. Furthermore, it was discovered that sputtering temperature of 120 °C created a desired power conversion energy (PCE) of 7.27% based on the J-V plot. Further increase of the sputtering temperature to 160 °C and 200 °C led to excessive TiO2 growth on the rGO nanosheet, thus resulting in undesirable charge recombination formed at the photoanode in the DSSC device.
The cytotoxic potency of a series of triphenyltin(IV) compounds of general composition [Ph3Sn(Ln)] (1-6) has been probed in vitro employing MDA-MB-231 (human breast cancer) and HeLa (human cervical cancer) cell lines, where Ln=L1-3; isomeric 2/3/4-{(E)-2-[4-(dimethylamino)phenyl]diazenyl}benzoates and L4-6are their corresponding isoelectronic imino analogues 2/3/4-[(E)-{[4-(dimethylamino)phenyl]methylidene}amino]benzoates. Compounds 1-6 have been characterized by elemental analysis and their spectroscopic properties were studied using IR and NMR (1H,13C,119Sn) techniques. The molecular structures of a pro-ligand 2-[(E)-{[4-(dimethylamino)phenyl]methylidene}amino]benzoic acid (HL4) and two representative molecules, Ph3Sn(L2) 2 and Ph3Sn(L5) 5, have been determined by X-ray crystallography. Structural analyses of 2 and 5 revealed distorted tetrahedral geometries within C3O donor sets owing to monodentate modes of coordination of the respective carboxylate ligands, close intramolecular Sn…O(carbonyl) interactions notwithstanding. Cytotoxic studies in vitro in MDA-MB-231 and HeLa cell lines revealed high activity, in sub-micromolar range, for all investigated compounds. Among these, 1 and 3 exhibited potent cytotoxicity most effectively towards MDA-MB-231 cells with a IC50value of 1.19 and 1.44μM, respectively, whereas 5 showed remarkable activity towards HeLa cells with a IC50value of 0.88μM, yet the series of compounds had minimal cytotoxic effect on normal HEK 293 (human embryonic kidney) cell line. The underlying investigation suggested that the compounds exert potent antitumor effect by elevating intracellular reactive oxygen species generation and cause delay in cell cycle by inhibiting cells at G2/M phase. The results presented herein suggest further development of this class of triphenyltin(IV) compounds-based drugs as potential anti-cancer therapies should be pursued.
Two independent molecules that differ in terms of rotation about the central S-N bond comprise the asymmetric unit of the title compound 1. The molecules have a V-shape with the dihedral angles between the fused ring system and benzene ring being 79.08(6)° and 72.83(5)°, respectively. The packing is mostly driven by p···p interactions occurring between the tolyl ring of one molecule and the C6 ring of the indole fused ring system of the other. DFT and IRC calculations for these and related 1-(arylsulfonyl)indole molecules showed that the rotational barrier about the S-N bond between conformers is within the 2.5-5.5 kcal/mol range. Crystal data for C16H13NO3S (1): Mr = 299.33, space group Pna21, a = 19.6152(4) Å, b = 11.2736(4) Å, c = 12.6334(3) Å, V = 2793.67(13) Å3, Z = 8, Z' = 2, R = 0.034.
The synthesis and characterisation of R3PAu[S2CN((i)Pr)CH2CH2OH], for R = Ph (1), Cy (2) and Et (3)4, is reported. Compounds 1-3 are cytotoxic against the doxorubicin-resistant breast cancer cell line, MCF-7R, with 1 exhibiting greater potency and cytotoxicity than either of doxorubicin and cisplatin. Based on human apoptosis PCR-array analysis, caspase activities, DNA fragmentation, cell apoptotic assays, intracellular reactive oxygen species (ROS) measurements and human topoisomerase I inhibition, induction of apoptosis by 1, and necrosis by 2 and 3, are demonstrated, by both extrinsic and intrinsic pathways. Compound 1 activates the p53 gene, 2 activates only the p73 gene, whereas 3 activates both the p53 and p73 genes. Compounds 1 and 3 activate NF-κB, and each inhibits topoisomerase I.
The X-ray single crystal analysis of isomeric ortho, meta, and para bromo-substituted α-methylsulfonyl-α-diethoxyphosphoryl acetophenones showed that this class of compound adopts synclinal (gauche) conformations for both [-P(O)(OEt)2] and [-S(O)2Me] groups, with respect to the carbonyl functional group. The phosphonate, sulfonyl, and carbonyl functional groups are joined through an intramolecular network of attractive interactions, as detected by molecular orbital calculations at the M06-2X/6-31G(d,p) level. These interactions are responsible for the more stable conformations in the gas phase, which also persist in the solid-state structures. The main structural distinction in the title compounds relates to the torsion angle of the aryl group (with respect to the carbonyl group), which gives rise to different interactions in the crystal packing, due to the different positions of the Br atom.
The phosphanegold(I) carbonimidothioates, Ph3PAu{SC(OR)=NC6H4Me-4} for R = Me (1), Et (2) and iPr (3), feature linear P-Au-S coordination geometries and exhibit potent in vitro cytotoxicity against HT-29 colon cancer cells in both monolayer and multi-cellular spheroid models (e.g., IC50 = 11.9 ± 0.4 and 20.3 ± 0.3 μM for 2, respectively). Both intrinsic and extrinsic pathways of apoptosis are demonstrated by human apoptosis PCR array analysis, caspase activities, DNA fragmentation and cell apoptotic assays. Compounds 1-3 induce an extrinsic pathway that leads to down-regulation of NFκB. Compound 2 also exhibits an extrinsic apoptotic pathway involving the activation of both p53 and p73, whereas 3 activates p53 only. Lys48- and Lys63-linked polyubiquitination are also promoted by 1-3. Each of cytotoxic Ph3PAu{SC(OR)=NC6H4Me-4}, for R = Me (1), Et (2) and iPr (3), induce an intrinsic apoptotic pathway as well as an extrinsic pathway leading to down-regulation of NFκB. Lys48- and Lys63-linked polyubiquitination are promoted by 1-3 and these are able to inhibit cell invasion and to suppress the activity of TrxR.
2α,3α,24-Thrihydroxyurs-12-en-28-oicacid (TEOA), a pentacyclic triterpenoid, isolated from the roots of Actinidia eriantha, exhibits significant cytotoxicity against SW620, BGC-823, HepG-2, A549 and PC-3 cancer cells. In this study, we investigated the underlying molecular mechanism of the anticancer activity of TEOA in SW620 cells. We demonstrated that TEOA induced apoptosis through cleavage of caspase-9 and PARP in SW620 cells. In addition, evidence of TEOA-mediated autophagy included the induction of autophagolysosomes and activation of autophagic markers LC-3B and p62. Further analysis illustrated that TEOA promoted the phosphorylation of PERK and elF2α, followed by up-regulation of the downstream protein CHOP, suggesting the involvement of PERK/eIF2α/CHOP pathway and ER stress in TEOA-induced autophagy in SW620 cells. Meanwhile, TEOA-mediated PINK1, Parkin, ubiquitin and p62 activation revealed that TEOA induced specific autophagy-mitophagy in SW620 cells. Additionally, an antioxidant NAC attenuated the TEOA-induced mitophagy, indicating that TEOA triggers mitophagy via a ROS-dependent pathway. Collectively, our findings revealed a novel cellular mechanism of TEOA in the colon cancer cell line SW620, thus providing a molecular basis for developing TEOA into an anti-tumor candidate.
Complete degradation of azo dye has always been a challenge due to the refractory nature of azo dye. An innovative hybrid system, constructed wetland-microbial fuel cell (CW-MFC) was developed for simultaneous azo dye remediation and energy recovery. This study investigated the effect of circuit connection and the influence of azo dye molecular structures on the degradation rate of azo dye and bioelectricity generation. The closed circuit system exhibited higher chemical oxygen demand (COD) removal and decolourisation efficiencies compared to the open circuit system. The wastewater treatment performances of different operating systems were ranked in the decreasing order of CW-MFC (R1 planted-closed circuit) > MFC (R2 plant-free-closed circuit) > CW (R1 planted-open circuit) > bioreactor (R2 plant-free-open circuit). The highest decolourisation rate was achieved by Acid Red 18 (AR18), 96%, followed by Acid Orange 7 (AO7), 67% and Congo Red (CR), 60%. The voltage outputs of the three azo dyes were ranked in the decreasing order of AR18 > AO7 > CR. The results disclosed that the decolourisation performance was significantly influenced by the azo dye structure and the moieties at the proximity of azo bond; the naphthol type azo dye with a lower number of azo bond and more electron-withdrawing groups could cause azo bond to be more electrophilic and more reductive for decolourisation. Moreover, the degradation pathway of AR18, AO7 and CR were elucidated based on the respective dye intermediate products identified through UV-Vis spectrophotometry, high-performance liquid chromatography (HPLC), and gas chromatograph-mass spectrometer (GC-MS) analyses. The CW-MFC system demonstrated high capability of decolouring azo dyes at the anaerobic anodic region and further mineralising dye intermediates at the aerobic cathodic region to less harmful or non-toxic products.
The n-butyramido, isobutyramido, benzamido, and furancarboxamido functions profoundly modulate the electronics of the stilbene olefinic and NH groups and the corresponding radical cations in ways that influence the efficiency of the cyclization due presumably to conformational and stereoelectronic factors. For example, isobutyramido- stilbene undergoes FeCl(3) promoted cyclization to produce only indoline, while n-butyramidostilbene, under the same conditions, produces both indoline and bisindoline.
Dunaliine A (1), a new amino diketone, has been isolated from the leaves of Desmos dunalii together with four known dihydrochalcones: 2',4-dihydroxy-4',6'-dimethoxy-3',5'-dimethyldihydrochalcone (2), 2',4-dihydroxy-4',6'-dimethoxydihydrochalcone (3), 2',4-dihydroxy-4',5',6'-trimethoxydihydrochalcone (4) and 2',4-dihydroxy-5'-methyl-4',6'-dimethoxydihydrochalcone (5). The structures of these compounds were established notably by spectral analysis (1D- and 2D- (1)H, (13)C NMR), UV, IR and HRMS.
A new dibenzotetraaza[14]annulene bearing two 3,3-dimethylindolenine fragments at the meso positions (LH(2)), has been synthesized through a nontemplate method. X-ray crystallography shows that the whole molecule is planar. The basicity of the indolenine ring permits the macrocycle to be protonated external to the core and form LH(4)(2+)·2Cl(-). Yet another structural modification having strong C-H···π interactions was found in the chloroform solvate of LH(2). The latter two modifications are accompanied by a degree of nonplanar distortion. The antiaromatic core of the macrocycle can accommodate a number of metal ions, Mn(III), Fe(III), Co(II), Ni(II) and Cu(II), to form complexes of [Mn(L)Br], [Mn(L)Cl], [Fe(LH(2))Cl(2)](+)·Cl(-), [Co(L)], [Ni(L)], and [Cu(L)]. In addition, the reaction of LH(2) with the larger Pd(II) ion leads to the formation of [Pd(2)(LH(2))(2)(OAc)(4)] wherein the macrocycle acts as a semiflexible ditopic ligand to coordinate pairs of metal ions via its indolenine N atoms into dinuclear metallocycles. The compounds LH(2), [Co(L)], and [Ni(L)] are isostructural and feature close π-stacking as well as linear chain arrangements in the case of the metal complexes. Variable temperature magnetic susceptibility measurements showed thermally induced paramagnetism in [Ni(L)].
The stereoselective reaction of an allyl bromide with an aldehyde mediated by a low valency bismuth species was the key reaction in stereoselective syntheses of (4S,6R,8R,10S,16S)- and (4S,6R,8R,10S,16R)-4,6,8,10,16-pentamethyldocosanes. (13)C NMR data for these compounds confirmed that the cuticular hydrocarbon isolated from the cane beetle Antitrogus parvulus was the (4S,6R,8R,10S,16S)-stereoisomer.
Mast cells (MCs), a type of immune effector cell, have recently become recognized for their ability to cause vascular leakage during dengue virus (DENV) infection. Although MC stabilizers have been reported to attenuate DENV induced infection in animal studies, there are limited in vitro studies on the use of MC stabilizers against DENV induced MC degranulation. 2,4,6-trihydroxy-3-geranyl acetophenone (tHGA) has been reported to be a potential MC stabilizer by inhibiting IgE-mediated MC activation in both cellular and animal models. The present study aims to establish an in vitro model of DENV3-induced RBL-2H3 cells using ketotifen fumarate as a control drug, as well as to determine the effect of tHGA on the release of MC mediators upon DENV infection. Our results demonstrated that the optimal multiplicities of infection (MOI) were 0.4 × 10-2 and 0.8 × 10-2 focus forming units (FFU)/cell. Ketotifen fumarate was proven to attenuate DENV3-induced RBL-2H3 cells degranulation in this in vitro model. In contrast, tHGA was unable to attenuate the release of both β-hexosaminidase and tumor necrosis factor (TNF)-α. Nonetheless, our study has successfully established an in vitro model of DENV3-induced RBL-2H3 cells, which might be useful for the screening of potential MC stabilizers for anti-dengue therapies.