Toxicity Measurement of Imidazolium Ionic Liquids Using Acute Toxicity Test

Ionic liquids (ILs) can be considered as environmentally friendly solvent, but they have the ability to dissolve in water and accumulate in the environment. Therefore, the toxicity of ILs should be assessed in order to prevent their harm to human and environment. This study was carried out to investigate the toxicity of ILs towards marine and freshwater fish. Three ILs have been tested, which are 1-Butyl-3-methylimidazolium hydrogen sulfate and 1-Butyl-3-methylimidazolium bis (trifluoromethylsulfonyl) imide toward marine fish and 1-Hexyl-3-methylimidazolium bis (trifluoromethylsulfonyl) imide toward freshwater fish. Two different marine fish were employed, which are: Cephalopholis cruentata (grouper) and Lates calcarifer (barramundi). For freshwater fish, male Poecilia reticulate (guppy) was employed. The toxicity tests were conducted according to OECD (Organisation for Economic Cooperation and Development) guideline 203. For 1-Butyl-3-methylimidazolium hydrogen sulphate [BMIM][HSO4], the median lethal concentration (LC50) estimated toward Cephalopholis cruentatato be 199.98 mg.L^-1. For 1-Butyl-3-methylimidazolium bis (trifluoromethylsulfonyl) imide [BMIM][TFSI], LC50 estimated toward LatesCalcariferto be 374.11 mg.L^-1. While, for 1-Hexyl-3-methylimidazolium bis (trifluoromethylsulfonyl) imide, [HMIM][NTf2], LC50 estimated toward Poecilia Reticulate to be 207.49 mg.L^-1. All the LC50 values obtained can be identified as practically nontoxic liquids based on Acute Toxicity Rating Scale by Fish and Wildlife Service (FWS). As to our knowledge, there is no previous reported toxicity studies of [BMIM][HSO4] and [BMIM][TFSI] on marine fish and [HMIM] [NTf2] on freshwater fish. Thus, this paper can be used as a benchmark for researchers who are dealing with these three ILs.     

Fluorinated Nanocarbons Cytotoxicity

As the research in nanotechnology progresses, there will eventually be an influx in the number of commercial products containing different types of nanomaterials. This phenomenon might damage our health and environment if the nanomaterials used are found to be toxic and they are released into the waters when the products degrade. In this study, we investigated the cytotoxicity of fluorinated nanocarbons (CXFs), a group of nanomaterials which can find applications in solid lubricants and lithium primary batteries. Our cell viability findings indicated that the toxicological effects induced by the CXF are dependent on the dose, size, shape, and fluorine content of the CXF. In addition, we verified that CXFs have insignificant interactions with the cell viability assays—methylthiazolyldiphenyl‐tetrazolium bromide (MTT) and water‐soluble tetrazolium salt (WST‐8), thus suggesting that the cytotoxicity data obtained are unlikely to be affected by CXF‐induced artifacts and the results will be reliable.     

The molecular basis of myeloid malignancies

Myeloid malignancies consist of acute myeloid leukemia (AML), myelodysplastic syndromes (MDS) and myeloproliferative neoplasm (MPN). The latter two diseases have preleukemic features and frequently evolve to AML. As with solid tumors, multiple mutations are required for leukemogenesis. A decade ago, these gene alterations were subdivided into two categories: class I mutations stimulating cell growth or inhibiting apoptosis; and class II mutations that hamper differentiation of hematopoietic cells. In mouse models, class I mutations such as the Bcr-Abl fusion kinase induce MPN by themselves and some class II mutations such as Runx1 mutations induce MDS. Combinations of class I and class II mutations induce AML in a variety of mouse models. Thus, it was postulated that hematopoietic cells whose differentiation is blocked by class II mutations would autonomously proliferate with class I mutations leading to the development of leukemia. Recent progress in high-speed sequencing has enabled efficient identification of novel mutations in a variety of molecules including epigenetic factors, splicing factors, signaling molecules and proteins in the cohesin complex; most of these are not categorized as either class I or class II mutations. The functional consequences of these mutations are now being extensively investigated. In this article, we will review the molecular basis of hematological malignancies, focusing on mouse models and the interfaces between these models and clinical findings, and revisit the classical class I/II hypothesis.     

Forced degradation studies of lansoprazole using LC‐ESI HRMS and 1H‐NMR experiments: in vitro toxicity evaluation of major degradation products

Regulatory agencies from all over the world have set up stringent guidelines with regard to drug degradation products due to their toxic effects or carcinogenicity. Lansoprazole, a proton‐pump inhibitor, was subjected to forced degradation studies as per ICH guidelines Q1A (R2). The drug was found to degrade under acidic, basic, neutral hydrolysis and oxidative stress conditions, whereas it was found to be stable under thermal and photolytic conditions. The chromatographic separation of the drug and its degradation products were achieved on a Hiber Purospher, C18 (250 × 4.6 mm, 5 μ) column using 10 mM ammonium acetate and acetonitrile as a mobile phase in a gradient elution mode at a flow rate of 1.0 ml/min. The eight degradation products (DP1–8) were identified and characterized by UPLC/ESI/HRMS with in‐source CID experiments combined with accurate mass measurements. DP‐1, DP‐2 and DP‐3 were formed in acidic, DP‐4 in basic, DP‐5 in neutral and DP‐1, DP‐6, DP‐7 and DP‐8 were in oxidation stress condition Among eight degradation products, five were hitherto unknown degradation products. In addition, one of the major degradation products, DP‐2, was isolated by using semi preparative HPLC and other two, DP‐6 and DP‐7 were synthesized. The cytotoxic effect of these degradation products (DP‐2, DP‐6 and DP‐7) were tested on normal human cells such as HEK 293 (embryonic kidney cells) and RWPE‐1(normal prostate epithelial cells) by MTT assay. From the results of cytotoxicity, it was found that lansoprazole as well as its degradation products (DP‐2, DP‐6 and DP‐7) were nontoxic up to 50‐μM concentrations, and the latter showed slightly higher cytotoxicity when compared with that of lansoprazole. DNA binding studies using spectroscopic techniques indicate that DP‐2, DP‐6 and DP‐7 molecules interact with ctDNA and may bind to its surface. Copyright © 2017 John Wiley & Sons, Ltd.     

Syntheses,toxicity and biodistribution of CO‐releasing molecules containing M(CO)5 (M = Mo,W and Cr)

A series of CO‐releasing molecules M(CO)₅ L (M = Mo, W and Cr), ( 1 , 2 , 3 , L = glycine methyl ester; 4 , 5 , 6 , N‐methylimidazole; 7 , 8 , 9 , 2‐aminopyridine; 10 , 11 , 12 , 3‐aminopyridine; 13 , 14 , 15 , 4‐aminopyridine), were synthesized. All complexes have been characterized by NMR, IR and electrospray ionization mass spectroscopy; the octahedral structures of 14 and 15 were also established by X‐ray crystallography. Furthermore, all complexes were evaluated for toxicity, pharmacokinetics and metabolic processes. Cytotoxic effects on the proliferation of fibroblast cell line were assayed by MTT. Among the complexes, Mo complex 1 showed the lowest cytotoxicity (IC₅₀ = 597 µmol l^?1) and W complex 2 showed a remarkable toxic effect, with IC₅₀ = 52 µmol l^?1. With the same ligand, the toxic effects of the complexes increase in the order of metal element W < Cr < Mo. For the same central metal element, the complexes containing imidazole showed lower toxic effects than those containing amino acid ester or aminopyridine. In accordance with the results from cytotoxicity, the complexes also showed corresponding toxic effects in animal models. The biodistributions of the complexes were established by inductively coupled plasma–atomic emission spectroscopy, measuring metal in tissues and organs. The results show that the complexes were gradually absorbed and unevenly distributed in vivo. The complexes containing imidazole entered tissues and organs faster than those containing amino acid ester. The complexes containing W atom were absorbed and distributed more slowly than those containing Mo or Cr atoms. Copyright © 2014 John Wiley & Sons, Ltd.     

Characterization of the photodegradation products of metolachlor: structural elucidation,potential toxicity and persistence

Aqueous solutions of metolachlor and metolachlor‐d₆ were photolyzed with UV‐visible radiations. The structures of 15 by‐products of metolachlor were determined through gas chromatography‐mass spectrometry analyses using electron and chemical ionization combined with multistage mass spectrometry. The photolysis by‐products of metolachlor resulted mainly from dehalogenation and hydroxylation, in some cases accompanied by cyclization. In silico tests for toxicity prediction showed that the toxicity of some photolysis products is expected to be greater than that of metolachlor. Persistence studies showed that the by‐product relative abundances vary in large amounts with the irradiation time. The post‐photolysis evolution of the solution was also studied, in order to determine the persistence of the main by‐products. It allowed to establish that most of the by‐products can be found more than 12 h after the end of the photolysis, which is of a great concern as treated water is generally available for consumption only a few hours after treatment in most of industrial processes. Copyright © 2012 John Wiley & Sons, Ltd.     

Toxicity Test n-Hexane: Ethyl Acetate (3:7) Fraction of Sudamala (Artemisia vulgaris L.)

Sudamala (Artemisia vulgaris L.) is commonly used in the community as anti-tumor in digestive organ, including in oral cavity. However, there have been no scientific studies about oral anti-carcinogenic active substances of Sudamala. The purpose of this study was to analyse the effect of per oral administration of n-hexane: ethyl acetate (3:7) fraction of Artemisia vulgaris L. on healthy mice. This experimental study used male Swiss Webster (Balb C) strain mice (Mus musculus) 2.5 months old, 20-30 grams by weight. Group 1, the mice received 0.5% CMC- Na fraction solvent, as a control. Group 2, the mice received 200 mg/kgbw n-hexane: ethyl acetate (3:7) fraction of Sudamala (Artemisia vulgaris L). The fraction was given once daily for 8 weeks per oral according to the mice's weight. At the end of 8^th week, the mice were killed and oral mucosal tissue was taken for biopsy specimens. Tunnel assay for Apoptosis and immunohistochemistry were undertaken for PCNA. T test analysis showed there was no significant difference between control and treatment groups. The fractions of n-hexane: ethyl acetate (3:7) of Sudamala (Artemisia vulgaris L) was not toxic, it was not harmful to living tissue in healthy mice.     

克林沙星酰胺衍生物的简易合成及其体内外生物活性

通过特色羧酸与克林沙星吡咯环氨基直接反应,得到19个未见文献报道的克林沙星酰胺衍生物,产物收率52.8%～97.5%.目标分子结构得到1H NMR,13C NMR,HR MS的确证.在琼脂扩散法初筛的基础上进行MIC活性验证,进而对活性较好的化合物开展急性毒性试验以及化合物稳定性实验,由此发现了抗菌活性更强、毒性更低、...     

Bioactive Tryptophan-Based Copper Complex with Auxiliary β-Carboline Spectacle Potential on Human Breast Cancer Cells: In Vitro and In Vivo Studies

Biocompatible tryptophan-derived copper (1) and zinc (2) complexes with norharmane (β-carboline) were designed, synthesized, characterized, and evaluated for the potential anticancer activity in vitro and in vivo. The in vitro cytotoxicity of both complexes 1 and 2 were assessed against two cancerous cells: (human breast cancer) MCF7 and (liver hepatocellular cancer) HepG2 cells with a non-tumorigenic: (human embryonic kidney) HEK293 cells. The results exhibited a potentially decent selectivity of 1 against MCF7 cells with an IC₅₀ value of 7.8 ± 0.4 μM compared to 2 (less active, IC₅₀ ~ 20 μM). Furthermore, we analyzed the level of glutathione, lipid peroxidation, and visualized ROS generation to get an insight into the mechanistic pathway and witnessed oxidative stress. These in vitro results were ascertained by in vivo experiments, which also supported the free radical-mediated oxidative stress. The comet assay confirmed the oxidative stress that leads to DNA damage. The histopathology of the liver also ascertained the low toxicity of 1.