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Fulltext Hydroxyl Functionalized Pyridinium Ionic Liquids: Experimental and Theoretical Study on Physicochemical and Electrochemical Properties

Lethesh KC, Evjen S, Raj JJ, Roux DCD, Venkatraman V, Jayasayee K, et al.

Front Chem, 2019;7:625.
PMID: 31620423 DOI: 10.3389/fchem.2019.00625

Structurally modified hydroxyl functionalized pyridinium ionic liquids (ILs), liquid at room temperature, were synthesized and characterized. Alkylated N-(2-hydroxyethyl)-pyridinium ILs were prepared from alkylpyridines via corresponding bromide salts by N-alkylation (65-93%) and final anion exchange (75-96%). Pyridinium-alkylation strongly influenced the IL physicochemical and electrochemical properties. Experimental values for the ILs physicochemical properties (density, viscosity, conductivity, and thermal decomposition temperature), were in good agreement with corresponding predicted values obtained by theoretical calculations. The pyridinium ILs have electrochemical window of 3.0-5.4 V and were thermally stable up to 405°C. The IL viscosity and density were measured over a wide temperature range (25-80°C). Pyridine alkyl-substitution strongly affected the partial positive charge on the nitrogen atom of the pyridinium cations, as shown by charge distribution calculations. On-going studies on Mg complexes of the new ILs demonstrate promising properties for high current density electrodeposition of magnesium.

Matched MeSH terms: Alkylating Agents
Fulltext Investigating the potential of Nigella Sativa and Thymoquinone in salvaging the Embryo from effects of Toxic Paternal Exposure to Cyclophosphamide

Suzanah Abdul Rahman, Nadia Hanis Abdul Samat, Nur Amalina Ahmad, ‘Afif Raihan Abdullah, Syazana Mohamad Zahri, Saheera Kamarzaman

International Medical Journal Malaysia, 2017;16(1):99-106.
MyJurnal

Exposure to cyclophosphamide (CPA) for cancer treatment results in over-production of reactive oxygen species and oxidative stress thus affecting the DNA in male germ cell inducing sperm defects. Our goal is to assess the potential effects of Nigella sativa extract (NSE) and thymoquinone (TQ) on sperm and embryo quality following fertlization of sperm produced from germ cells which have been exposed to the damaging alkylating effects of CPA.

Matched MeSH terms: Alkylating Agents
Fulltext Scanning the effects of ethyl methanesulfonate on the whole genome of Lotus japonicus using second-generation sequencing analysis

Mohd-Yusoff NF, Ruperao P, Tomoyoshi NE, Edwards D, Gresshoff PM, Biswas B, et al.

G3 (Bethesda), 2015 Apr;5(4):559-67.
PMID: 25660167 DOI: 10.1534/g3.114.014571

Genetic structure can be altered by chemical mutagenesis, which is a common method applied in molecular biology and genetics. Second-generation sequencing provides a platform to reveal base alterations occurring in the whole genome due to mutagenesis. A model legume, Lotus japonicus ecotype Miyakojima, was chemically mutated with alkylating ethyl methanesulfonate (EMS) for the scanning of DNA lesions throughout the genome. Using second-generation sequencing, two individually mutated third-generation progeny (M3, named AM and AS) were sequenced and analyzed to identify single nucleotide polymorphisms and reveal the effects of EMS on nucleotide sequences in these mutant genomes. Single-nucleotide polymorphisms were found in every 208 kb (AS) and 202 kb (AM) with a bias mutation of G/C-to-A/T changes at low percentage. Most mutations were intergenic. The mutation spectrum of the genomes was comparable in their individual chromosomes; however, each mutated genome has unique alterations, which are useful to identify causal mutations for their phenotypic changes. The data obtained demonstrate that whole genomic sequencing is applicable as a high-throughput tool to investigate genomic changes due to mutagenesis. The identification of these single-point mutations will facilitate the identification of phenotypically causative mutations in EMS-mutated germplasm.

Matched MeSH terms: Alkylating Agents/chemistry*
Structure of the d(CGCGAATTCGCG)2 complex of the minor groove binding alkylating agent alkamin studied by mass spectrometry

Majid AM, Smythe G, Denny WA, Wakelin LP

Mol. Pharmacol., 2007 Apr;71(4):1165-78.
PMID: 17251328

Nitrogen mustard alkylating agents are important cancer drugs. Much interest has been focused on redirecting their covalent adducts from the N7 atoms of guanine in the major groove of DNA to the N3 atoms of adenine in the minor groove by attaching mustard groups to AT-selective minor groove binding ligands. Here we describe the use of electrospray ionization and matrix-assisted laser desorption ionization/time-of-flight mass spectrometry to study the structure of the DNA complexes of two minor groove binding polybenzamide mustards, alkamin and alkamini; the former is a bis-half-mustard in which reactive groups are disposed at each end of the ligand, and the latter is its monofunctional analog. Alkamin is potently cytotoxic and active in experimental mouse tumor models, whereas alkamini is not. We have studied their interaction with the DNA dodecamer d(CGCGAATTCGCG)(2), designated A2T2, and we provide a detailed analysis of the observed DNA-ligand adduct ions and their fragmentation products. We find that alkamini alkylates A2T2 at guanine G4 and adenines A5 and A6 in a manner consistent with covalent attack on purine N3 atoms from the minor groove of the AT tract. Alkamin also forms monofunctional adducts at G4 and both adenines in which the second mustard arm is hydrolyzed but, in addition, forms a variety of interstrand cross-links between adenines A5/A6 and A5'/A6', an interstrand cross-link between G4 and A6', and an intrastrand cross-link between G4 and A6. We conclude that the marked cytotoxicity of alkamin and its experimental antitumor activity could be the consequence of its ability to cross-link cellular DNA at AT tract sequences.

Matched MeSH terms: Alkylating Agents/pharmacokinetics
Fulltext Biochemical and molecular aspects of 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis: a review

Venkatachalam K, Vinayagam R, Arokia Vijaya Anand M, Isa NM, Ponnaiyan R

Toxicol Res (Camb), 2020 Feb;9(1):2-18.
PMID: 32440334 DOI: 10.1093/toxres/tfaa004

1,2-dimethylhydrazine (DMH) is a member in the class of hydrazines, strong DNA alkylating agent, naturally present in cycads. DMH is widely used as a carcinogen to induce colon cancer in animal models. Exploration of DMH-induced colon carcinogenesis in rodent models provides the knowledge to perceive the biochemical, molecular, and histological mechanisms of different stages of colon carcinogenesis. The procarcinogen DMH, after a series of metabolic reactions, finally reaches the colon, there produces the ultimate carcinogen and reactive oxygen species (ROS), which further alkylate the DNA and initiate the development of colon carcinogenesis. The preneolpastic lesions and histopathological observations of DMH-induced colon tumors may provide typical understanding about the disease in rodents and humans. In addition, this review discusses about the action of biotransformation and antioxidant enzymes involved in DMH intoxication. This understanding is essential to accurately identify and interpret alterations that occur in the colonic mucosa when evaluating natural or pharmacological compounds in DMH-induced animal colon carcinogenesis.

Matched MeSH terms: Alkylating Agents
Fulltext Price variation among different brands of anticancer medicines available in hospital pharmacies of Nepal

Shrestha S, Poudel RS, Kc B, Poudel BK, Sapkota B, Sharma S, et al.

J Pharm Policy Pract, 2020;13:6.
PMID: 32266073 DOI: 10.1186/s40545-020-0203-0

Objective: To assess the variation in price among different brands of anticancer medicines available in hospital pharmacies at Nepalese cancer hospitals.
Methods: The price of different brands of the same anticancer medicines available in the hospital pharmacies of two cancer hospitals was assessed. Prices of different dosage forms such as a single tablet, capsule and vial were calculated. The difference in the maximum and minimum price of the same drug manufactured by different pharmaceutical industries was determined, and the percentage variation in price was calculated. The prices of medicines (brands) were also compared with the price determined by the government where available.
Results: Price variation was assessed for 31 anticancer medicines belonging to six broad categories. Prices were found to vary maximally among the following medicines, each belonging to separate categories: among alkylating agents, the price of temozolomide 100 mg capsule varied 308%; among antimetabolite agents, the price of pemetrexed 500 mg injection varied 134%; among hormonal drugs, the price of letrozole 2.5 mg tablet varied 200%; among antibody class, the price of trastuzumab 440 mg injection varied 73%; among natural products, the price of irinotecan 100 mg injection varied 590%; and among miscellaneous agents, the price of bortezomib 2 mg injection varied 241%. There was a significant difference in the mean MRP of the alkylating agents with the antimetabolites (p-value 0.006) and the monoclonal antibody (p-value

Matched MeSH terms: Alkylating Agents
Supplementation of selenium reduces chemical hepatocarcinogenesis in male Sprague-Dawley rats

Alwahaibi N, Mohamed J, Alhamadani A

J Trace Elem Med Biol, 2010 Apr;24(2):119-23.
PMID: 20413070 DOI: 10.1016/j.jtemb.2009.09.003

Selenium is an essential micronutrient mineral found mainly in soils and has been shown to prevent certain cancers in humans and animals. However, the dose and effects of selenium on liver cancer are controversial. The aim of this study was to investigate the effects of sodium selenite (4 mg/kg in drinking water) on chemically induced hepatocarcinogenesis in rats. Hepatocarcinogenesis was induced by a single intraperitoneal injection of diethyl nitrosamine (DEN) (200 mg/kg body weight) and 2 weeks later, the carcinogenic effect was promoted by 2-acetylaminofluorene (2-AAF) (0.02%). 44 Sprague-Dawley rats were divided into 6 groups: negative control, positive control (DEN+2-AAF), pre-selenium group (sodium selenite for 4 weeks, then DEN+2-AAF), pre-selenium control group (sodium selenite for 4 weeks, no DEN or 2-AAF), post-selenium group (sodium selenite for 8 weeks after 4 weeks of DEN injection) and post-selenium control group (sodium selenite for 8 weeks, no DEN or 2-AAF). Hematoxylin and eosin plus Gordon and Sweet's methods were used to stain liver tissues. The results showed that the number and sizes of hepatic nodules in pre- and post-selenium treatment groups significantly decreased (P<0.05) compared with the positive control. Microscopic analysis of pre- and post-selenium groups showed that the majority of nodules were hyperplastic with preserved liver architecture, whereas the positive control was full of neoplastic nodules with a completely disrupted liver architecture. Hence, pre- and post-selenium treatments can reduce the extent of liver cancer on chemically induced hepatocarcinogenesis in rats.

Matched MeSH terms: Alkylating Agents/toxicity
Fulltext Evaluation of NMU-Induced Breast Cancer Treated with Sirolimus and Sunitinib on Breast Cancer Growth

Jaffar NFN, Muhammad Sakri MS, Jaafar H, Wan Abdul Rahman WF, Tengku Din TADA

Asian Pac J Cancer Prev, 2020 Oct 01;21(10):2919-2925.
PMID: 33112549 DOI: 10.31557/APJCP.2020.21.10.2919

OBJECTIVE: To analyze the effect of sirolimus and sunitinib in blocking the tumor growth and to evaluate the expressions of estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor-2 (HER2/neu) after treated with sirolimus and sunitinib.
METHODS: Thirty-two female Sprague Dawley rats at age 21-days old were administered intraperitoneally with N-Methyl-N-Nitroso Urea (NMU), dosed at 70mg/kg body weight. The rats were divided into 4 groups; Group 1 (Control, n=8), Group 2 (Sirolimus, n=8), Group 3 (Sunitinib, n=8) and Group 4 (Sirolimus+Sunitinib, n=8), being treated twice when the tumor reached the size of 14.5±0.5 mm and subsequently sacrificed after 5 days. The protein expressions of ER, PgR and HER2/neu of the tumor tissues were evaluated by using immunohistochemistry analysis.
RESULTS: Treatment with sirolimus alone lowered expressions of ER and PgR of breast cancer and reduced tumor size. There was no significant difference of ER and PgR expressions between control and sunitinib treated tumor. Sunitinib treated tumors reduce in diameter after the first treatment, however the diameter increases after the second treatment. Histologically, sunitinib treated tumor did not show any aggressive invasive carcinoma of no special type (NST) histological subtypes. In addition, all NMU-induced tumors are HER2/neu-negative scoring.
CONCLUSION: Sirolimus is neither synergistic nor additive with sunitinib for breast cancer treatment.
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Matched MeSH terms: Alkylating Agents/toxicity*
Cellular and Molecular Changes in MNU-Induced Breast Tumours Injected with PF4 or bFGF

Mohd Nafi SN, Idris F, Jaafar H

Asian Pac J Cancer Prev, 2017 Dec 28;18(12):3231-3238.
PMID: 29281877

Background: Angiogenic activity has been considered to reflect important molecular events during breast tumour
development. The present study concerned cellular and molecular changes of MNU-induced breast tumours subjected
to promotion and suppression of angiogenesis. Methods: Female Sprague Dawley rats at the age of 21 days received
MNU at the dose 70 mg/kg of body weight by intraperitoneal injection. Three months post-carcinogen initiation,
mammary tumours were palpated and their growth was monitored. When the tumour diameter reached 1.0 ± 0.05 cm,
rats were given bFGF or PF4 intratumourally at a dose of 10 μg/tumour. Entire palpable tumour were subsequently
excised and subjected to histology examination, IHC staining, and RT-PCR. Results: No critical morphological changes
were observed between pro-angiogenic factor, bFGF, and control groups. However, increase of tumour size with more
necrotic and diffuse areas was notable in tumours after anti-angiogenic PF4 intervention. ER and PR mRNA expression
was significantly up- and down-regulated in bFGF and PF4 groups, respectively. The trends were significantly associated
with peri- and intratumoural MVD counts. However, irrespective of whether we promoted or inhibited angiogenesis,
the expression of EGFR and ERBB2 continued to be significantly increased but this was not significantly associated
with the MVD score. No significant differences in E-cadherin and LR gene expression were noted between intervention
and control groups. Conclusion: ER and PR receptor expression shows consistent responses when tumour angiogenesis
is manipulated either positively or negatively. Our study adds to current understanding that not only do we need to
target hormonal receptors, as presently practiced, but we also need to target endothelial receptors to successfully treat
breast cancer.

Matched MeSH terms: Alkylating Agents/toxicity