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Ecotoxicology and Environmental Safety Sep 2021Alkyl-PAHs are the predominant form of PAHs in crude oils which are supposed to demonstrate different toxicities compared to non-alkyl PAHs. Little information is...
Alkyl-PAHs are the predominant form of PAHs in crude oils which are supposed to demonstrate different toxicities compared to non-alkyl PAHs. Little information is available about the toxicity of alkyl-PAHs on marine Artemia. This study addressed and compared the lethal, behavioral, growth and developmental toxicities of three alkyl-PAHs, namely 3-methyl phenanthrene (3-mPhe), retene (Ret) and 2-methyl anthracene (2-mAnt), to their non-alkyl forms, phenanthrene (Phe) and anthracene (Ant) using Artemia parthenogenetica (nauplii, <24 h) as test organism following a 48 h and a 7 d of exposure, respectively. Benzo-a-pyrene (Bap) was selected as a reference toxicant for the comparison with the above alkyl-PAHs and non-alkyl PAHs. Results showed that for all tested endpoints, A. parthenogenetica nauplii had the highest sensitivity to Bap while Ant had no significant effect on nauplii survival or development within given concentrations. Considering the aqueous freely dissolved PAH concentrations, the 48 h-LC (survival), 48 h-EC (immobility) and 7 d-LC (survival) of Bap were calculated as 0.321, 0.285 and 0.027 μg/L, respectively, which were twofold to fivefold lower than those of Phe, 3-mPhe, Ret, Ant and 2-mAnt. A higher acute toxicity of alkyl-PAHs (3-mPhe and 2-mAnt) than their non-alkyl forms (Phe and Ant) was observed. Not limited to Phe, the common non-polar narcotic mode of action was also observed for Bap, 3-mPhe, Ret and 2-mAnt, which was evident by the inhibited mobility of nauplii. The decreased body lengths were found for all PAH treatments compared to the solvent control, whereas instar retardations were only found in nauplii exposed to Bap, Phe and Ret. Our findings emphasized the sensitivity differences of A. parthenogenetica nauplii to selected alkyl PAHs and non-alkyl PAHs and confirmed the application of lethal, behavioral and growth indicators in the toxicity evaluation of selected PAHs other than Ant. However, the distinct toxicities of these PAHs suggested other toxic modes of action may play more important roles apart from narcotic mode of action and need to be elucidated in future studies. In addition, a strong correlation between the body length and the instar of A. parthenogenetica nauplii was observed for each PAH exposure, suggesting that body length can be representative for both growth and developmental indicators during biological monitoring of PAH pollution in marine environment.
Topics: Animals; Anthracenes; Artemia; Lethal Dose 50; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Water Pollutants, Chemical
PubMed: 34015631
DOI: 10.1016/j.ecoenv.2021.112302 -
Archives of Virology Aug 2021Influenza A virus (IAV) can cause high morbidity and mortality globally every year. Myriad host kinases and their related signaling pathways are involved in IAV...
Influenza A virus (IAV) can cause high morbidity and mortality globally every year. Myriad host kinases and their related signaling pathways are involved in IAV infection, and the important role of the c-Jun N-terminal kinase signaling pathway during infection has been demonstrated. SP600125, an inhibitor of c-Jun N-terminal kinase, was found in our previous study to suppress IAV replication in vitro. In this study, we established a mouse model of H1N1 IAV infection and treated the mice with SP600125 to study its protective effect. The results showed that SP600125 treatment reduced the pulmonary inflammatory response, lung injury, and pulmonary viral load and increased the survival rate of H1N1-infected mice. Our data confirm the crucial role of c-Jun N terminal kinase in H1N1 virus replication and inflammatory responses in vivo. Hence, we speculate that SP600125 has a potential antiviral therapeutic benefit against IAV infection.
Topics: Animals; Anthracenes; Disease Models, Animal; Female; Gene Expression Regulation; Influenza A Virus, H1N1 Subtype; Lung; Mice; Orthomyxoviridae Infections; Proto-Oncogene Proteins c-jun; Random Allocation; Treatment Outcome; Virus Replication
PubMed: 34014386
DOI: 10.1007/s00705-021-05103-0 -
Molecules (Basel, Switzerland) Apr 2020The biological active compound rishirilide B is produced by . The cosmid cos4 contains the complete rishirilide B biosynthesis gene cluster. Its heterologous expression...
The biological active compound rishirilide B is produced by . The cosmid cos4 contains the complete rishirilide B biosynthesis gene cluster. Its heterologous expression in the host J1074 led to the production of rishirilide B as a major compound and to small amounts of rishirilide A, rishirilide D and lupinacidin A. In order to gain more insights into the biosynthesis, gene inactivation experiments and gene expression experiments were carried out. This study lays the focus on the functional elucidation of the genes involved in the early biosynthetic pathway. A total of eight genes were deleted and six gene cassettes were generated. Rishirilide production was not strongly affected by mutations in and . The deletion of and led to the formation of polyketides with novel structures. These results indicated that RslK4 and RslO3 are involved in the generation or selection of the starter unit for rishirilide biosynthesis. In the mutant strain, two novel compounds were detected, which were also produced by a strain containing solely the genes , , , , and . and mutants predominately produce galvaquinones. Therefore, the ketoreductase RslO10 is involved in an early step of rishirilide biosynthesis and the oxygenases RslO1 and RslO4 are most probably acting on an anthracene moiety. This study led to the functional elucidation of several genes of the rishirilide pathway, including , which is involved in selecting the unusual starter unit for polyketide synthesis.
Topics: Anthracenes; Biosynthetic Pathways; Gene Deletion; Gene Expression Regulation, Bacterial; Genes, Bacterial; Molecular Structure; Multigene Family; Streptomyces
PubMed: 32340131
DOI: 10.3390/molecules25081955 -
Molecules (Basel, Switzerland) Apr 2021Hypericin (Hyp), well-known as an antidepressant, is mainly extracted from . Although Hyp accumulation and biomass are greater at lower compared to higher temperature,...
Hypericin (Hyp), well-known as an antidepressant, is mainly extracted from . Although Hyp accumulation and biomass are greater at lower compared to higher temperature, the regulation mechanism has not been reported. Here, the physiological characteristics and transcriptome of grown at 15 and 22 °C were determined and analyzed by HPLC and de novo sequencing. The results showed that the stomatal density and opening percentages were 1.1- and 1.4-fold more, and the Hyp content was 4.5-fold greater at 15 °C compared to 22 °C. A total of 1584 differentially expressed genes (DEGs) were observed at 15 versus 22 °C, with 749 characterized genes, 421 upregulated (UR) and 328 downregulated (DR). Based on biological functions, 150 genes were associated with Hyp biosynthesis, plant growth and the stress response, including photosynthesis, carbohydrate metabolism, fatty acids metabolism, cytochrome P450 (CYPs), morpho-physiological traits, heat shock proteins (HSPs), cold-responsive proteins (CRPs) and transcription factors (TFs). The differential expression levels of the master genes were confirmed by qRT-PCR and almost consistent with their Reads Per kb per Million (RPKM) values. This physiological and transcriptomic analyses provided insight into the regulation mechanisms of low temperature enhancing Hyp biosynthesis in .
Topics: Anthracenes; Gene Expression Profiling; Hypericum; Perylene; Temperature; Transcriptome
PubMed: 33921038
DOI: 10.3390/molecules26082294 -
ACS Applied Materials & Interfaces Mar 2022Hypericin is a photosensitizing drug that is active against membrane-enveloped viruses and therefore constitutes a promising candidate for the treatment of SARS-CoV-2...
Hypericin is a photosensitizing drug that is active against membrane-enveloped viruses and therefore constitutes a promising candidate for the treatment of SARS-CoV-2 infections. The antiviral efficacy of hypericin is largely determined by its affinity toward viral components and by the number of active molecules loaded on single viruses. Here we use an experimental approach to follow the interaction of hypericin with SARS-CoV-2, and we evaluate its antiviral efficacy, both in the dark and upon photoactivation. Binding to viral particles is directly visualized with fluorescence microscopy, and a strong affinity for the viral particles, most likely for the viral envelope, is measured spectroscopically. The loading of a maximum of approximately 30 molecules per viral particle is estimated, despite with marked heterogeneity among particles. Because of this interaction, nanomolar concentrations of photoactivated hypericin substantially reduce virus infectivity on Vero E6 cells, but a partial effect is also observed in dark conditions, suggesting multiple mechanisms of action for this drug.
Topics: Animals; Anthracenes; Antiviral Agents; Chlorocebus aethiops; Perylene; SARS-CoV-2; Vero Cells; COVID-19 Drug Treatment
PubMed: 35302731
DOI: 10.1021/acsami.1c22439 -
Molecules (Basel, Switzerland) Jul 2013Aminoanthraquinones were successfully synthesized via two reaction steps. 1,4-Dihydroxyanthraquinone (1) was first subjected to methylation, reduction and acylation to...
Aminoanthraquinones were successfully synthesized via two reaction steps. 1,4-Dihydroxyanthraquinone (1) was first subjected to methylation, reduction and acylation to give an excellent yield of anthracene-1,4-dione (3), 1,4-dimethoxyanthracene-9,10-dione (5) and 9,10-dioxo-9,10-dihydroanthracene-1,4-diyl diacetate (7). Treatment of 1, 3, 5 and 7 with BuNH2 in the presence of PhI(OAc)2 as catalyst produced seven aminoanthraquinone derivatives 1a, b, 3a, and 5a-d. Amination of 3 and 5 afforded three new aminoanthraquinones, namely 2-(butylamino)anthracene-1,4-dione (3a), 2-(butylamino)anthracene-9,10-dione (5a) and 2,3-(dibutylamino)anthracene-9,10-dione (5b). All newly synthesised aminoanthraquinones were examined for their cytotoxic activity against MCF-7 (estrogen receptor positive human breast) and Hep-G2 (human hepatocellular liver carcinoma) cancer cells using MTT assay. Aminoanthraquinones 3a, 5a and 5b exhibited strong cytotoxicity towards both cancer cell lines (IC50 1.1-13.0 µg/mL).
Topics: Anthraquinones; Cell Proliferation; Hep G2 Cells; Humans; MCF-7 Cells; Molecular Structure; Structure-Activity Relationship
PubMed: 23884135
DOI: 10.3390/molecules18078046 -
Asian Pacific Journal of Cancer... May 2022Breast cancer (BC) currently has no effective treatment especially for the highly aggressive and metastatic triple negative breast cancer (TNBC). Here, we investigated...
OBJECTIVE
Breast cancer (BC) currently has no effective treatment especially for the highly aggressive and metastatic triple negative breast cancer (TNBC). Here, we investigated the antitumoral and antimigratory effects of hypericin (HYP) encapsulated on Pluronic F127 (F127/HYP) photodynamic therapy (PDT) against TNBC cell line MDA-MB-231 compared to a nontumorigenic human breast ductal cell line (MCF-10A).
METHODS
The phototoxicity/cytotoxicity was assessed by MTT assay, long-term cytotoxicity by clonogenic assay, cell uptake, subcellular distribution, and cellular oxidative stress by fluorescence microscopy, cell death with annexin V-FITC/propidium iodide, PDT mechanism using sodium azide and D-mannitol, and cell migration by wound-healing assay.
RESULTS
The treatment promoted phototoxic effect on tumor cell line in a dose-dependent and selective manner. Internalization of F127/HYP was efficient and accumulation occurred in the endoplasmic reticulum and mitochondria, resulting in cellular oxidative stress mainly by the type II mechanism, induced by necrosis. Furthermore, F127/HYP decreased colony formation and reduced the cell migration ability in MDA-MB-231 cells.
CONCLUSION
Our results suggest a potentially useful role of F127/HYP micelles as a platform for HYP delivery to more specifically and effectively treat TNBC.
Topics: Anthracenes; Humans; Perylene; Photochemotherapy; Poloxamer; Triple Negative Breast Neoplasms
PubMed: 35633560
DOI: 10.31557/APJCP.2022.23.5.1741 -
Theranostics 2013Hypericin has been widely studied as a potent photosensitizer for photodynamic therapy in both preclinical and clinical settings. Recently, hypericin has also been... (Review)
Review
Hypericin has been widely studied as a potent photosensitizer for photodynamic therapy in both preclinical and clinical settings. Recently, hypericin has also been discovered to have a specific avidity for necrotic tissue. This affinity is also observed in a series of radiolabeled derivatives of hypericin, including [(123)I]iodohypericin, [(124)I]iodohypericin, and [(131)I]iodohypericin. Hypericin, along with other necrosis-avid contrast agents, has been investigated for use in noninvasively targeting necrotic tissues in numerous disorders. Potential clinical applications of hypericin include the identification of acute myocardial infarction, evaluation of tissue viability, assessment of therapeutic responses to treatments, and interventional procedures for solid tumors. The mechanisms of necrosis avidity in hypericin remain to be fully elucidated, although several hypotheses have been suggested. In particular, it has been proposed that the necrosis avidity of hypericin is compound specific; for instance, cholesterol, phosphatidylserine, or phosphatidylethanolamine components in the phospholipid bilayer of cellular membranes may be the major targets for its observed selectivity. Further investigations are needed to identify the specific binding moiety that is responsible for the necrosis avidity of hypericin.
Topics: Anthracenes; Humans; Necrosis; Optical Imaging; Perylene; Staining and Labeling
PubMed: 24052807
DOI: 10.7150/thno.6650 -
Accounts of Chemical Research Dec 2008Self-assembly of small molecules into one-dimensional nanostructures offers many potential applications in electronically and biologically active materials. The recent...
Self-assembly of small molecules into one-dimensional nanostructures offers many potential applications in electronically and biologically active materials. The recent advances discussed in this Account demonstrate how researchers can use the fundamental principles of supramolecular chemistry to craft the size, shape, and internal structure of nanoscale objects. In each system described here, we used atomic force microscopy (AFM) and transmission electron microscopy (TEM) to study the assembly morphology. Circular dichroism, nuclear magnetic resonance, infrared, and optical spectroscopy provided additional information about the self-assembly behavior in solution at the molecular level. Dendron rod-coil molecules self-assemble into flat or helical ribbons. They can incorporate electronically conductive groups and can be mineralized with inorganic semiconductors. To understand the relative importance of each segment in forming the supramolecular structure, we synthetically modified the dendron, rod, and coil portions. The self-assembly depended on the generation number of the dendron, the number of hydrogen-bonding functions, and the length of the rod and coil segments. We formed chiral helices using a dendron-rod-coil molecule prepared from an enantiomerically enriched coil. Because helical nanostructures are important targets for use in biomaterials, nonlinear optics, and stereoselective catalysis, researchers would like to precisely control their shape and size. Tripeptide-containing peptide lipid molecules assemble into straight or twisted nanofibers in organic solvents. As seen by AFM, the sterics of bulky end groups can tune the helical pitch of these peptide lipid nanofibers in organic solvents. Furthermore, we demonstrated the potential for pitch control using trans-to-cis photoisomerization of a terminal azobenzene group. Other molecules called peptide amphiphiles (PAs) are known to assemble in water into cylindrical nanostructures that appear as nanofiber bundles. Surprisingly, TEM of a PA substituted by a nitrobenzyl group revealed assembly into quadruple helical fibers with a braided morphology. Upon photocleavage of this the nitrobenzyl group, the helices transform into single cylindrical nanofibers. Finally, inspired by the tobacco mosaic virus, we used a dumbbell-shaped, oligo(phenylene ethynylene) template to control the length of a PA nanofiber self-assembly (<10 nm). AFM showed complete disappearance of long nanofibers in the presence of this rigid-rod template. Results from quick-freeze/deep-etch TEM and dynamic light scattering demonstrated the templating behavior in aqueous solution. This strategy could provide a general method to control size the length of nonspherical supramolecular nanostructures.
Topics: Anthracenes; Microscopy, Atomic Force; Microscopy, Electron, Transmission; Nanostructures; Peptides; Stereoisomerism
PubMed: 18754628
DOI: 10.1021/ar8000926 -
PloS One 2014An established synchronous fluorimetry method was used for in situ investigation of the photodegradation of pyrene (PYR) and anthracene (ANT) adsorbed onto fresh leaves...
An established synchronous fluorimetry method was used for in situ investigation of the photodegradation of pyrene (PYR) and anthracene (ANT) adsorbed onto fresh leaves of the seedlings of two mangrove species, Aegiceras corniculatum (L.) Blanco (Ac) and Kandelia obovata (Ko) in multicomponent mixtures (mixture of the ANT and PYR). Experimental results indicated that photodegradation was the main transformation pathway for both ANT and PYR in multicomponent mixtures. The amount of the PAHs volatilizing from the leaf surfaces and entering the inner leaf tissues was negligible. Over a certain period of irradiation time, the photodegradation of both PYR and ANT adsorbed onto the leaves of Ac and Ko followed first-order kinetics, with faster rates being observed on Ac leaves. In addition, the photodegradation rate of PYR on the leaves of the mangrove species in multicomponent mixtures was much slower than that of adsorbed ANT. Compared with the PAHs adsorbed as single component, the photodegradation rate of ANT adsorbed in multicomponent mixtures was slower, while that of PYR was faster. Moreover, the photodegradation of PYR and ANT dissolved in water in multicomponent mixtures was investigated for comparison. The photodegradation rate on leaves was much slower than in water. Therefore, the physical-chemical properties of the substrate may strongly influence the photodegradation rate of adsorbed PAHs.
Topics: Anthracenes; Photolysis; Plant Leaves; Primulaceae; Pyrenes; Rhizophoraceae
PubMed: 25144741
DOI: 10.1371/journal.pone.0104903