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Topoisomerase II Inhibition by Antitumor Intercalators and Demethylepipodophyllotoxins
Published in Robert I. Glazer, Developments in Cancer Chemotherapy, 2019
Moreover, some 9-aminoacridines give little or no stimulation of cleavage, even though they do bind to DNA by intercalation; this is notably the case for 9-aminoacridine itself and for o-AMSA.45 It may be that the stimulation of cleavage depends on the geometry of the conformational effects on DNA that result from intercalation by different structural classes of drugs which are known to differ in the base-pair unwinding angle that accompanies their intercalation.48 The unwinding angle by itself, however, does not account for structural factors that determine the relevant aspects of DNA conformational distortion. This would still not explain the activity of the demethylepipodophyllotoxins since these compounds do not bind strongly to purified DNA. The demethylepipodophyllotoxins therefore most likely act by binding to a site on the enzyme. The possibility is not excluded that the intercalators act by binding to the enzyme or perhaps simultaneously to DNA and enzyme.
Disposition and Metabolism of Drugs of Dependence
Published in S.J. Mulé, Henry Brill, Chemical and Biological Aspects of Drug Dependence, 2019
N -oxide formation – The biotransformation of morphine to its TV-oxide has not been reported in normal circumstances. However, N -oxide has been shown to be a urinary metabolite in cancer patients treated with combinations of morphine, 2,4-diamino-5-phenyl thiazole or 1,2,3,4-tetrahydro-9-aminoacridine,115 possibly through the inhibition of major metabolic pathway or the inhibition of breakdown of N -oxide by the thiazole or acridine derivative. Formation of N -oxides of tertiary amines as intermediates or as an alternative pathway in oxidative N -dealkylation of drugs has previously been postulated.116,117N -oxide was not detected as a metabolite of morphine in the rat brain.70
Antimalarials
Published in Sarah H. Wakelin, Howard I. Maibach, Clive B. Archer, Handbook of Systemic Drug Treatment in Dermatology, 2015
Chloroquine and hydroxychloroquine are 4-aminoquinolones, while mepacrine (quinacrine), a 9-aminoacridine, has an extra benzene ring but is otherwise structurally similar. This structural change leads to a different side-effect profile. The mode of action of antimalarials in dermatological disease is still uncertain, although recent research has led to a clearer understanding of their mode of action. Antimalarials inhibit toll-like receptors, particularly TLR9 and TLR7, thus reducing levels of tumour necrosis factor (TNF)a and type 1 interferons, which are important mediators of inflammation in lupus. This probably has more relevance to their efficacy than the previously reported actions on phago/lysosomal function and interruption of antigen processing.
Investigation of radiation protective features of azadispiro derivatives and their genotoxic potential with Ames/Salmonella test system
Published in International Journal of Radiation Biology, 2023
Burak Alaylar, Bünyamin Aygün, Kadir Turhan, Mehmet Karadayı, Esra Cinan, Zuhal Turgut, Gökçe Karadayı, Mohammed Ibrahim Abu Al-Sayyed, Medine Güllüce, Abdulhalik Karabulut
The tester strains Salmonella typhimurium TA97a, TA98, TA100 from Moltox® Inc., Boone (NC, USA) and TA1535, and TA1537 were provided from The American Type Culture Collection (ATCC®), Bacteria Department of Georgetown University (Washington-USA). The stock solutions were stored at −87 °C for further studies. For Ames/Salmonella assay, the working cultures were obtained from the stock solutions and inoculated into a nutrient broth medium for incubation at 37 °C an overnight (Tuğcu et al. 2018). Besides, 9-aminoacridine (9-AA), 4-nitro-o-phenylenediamine (4-NPD), and sodium azide (NaN3) were bought from ABCR GmbH & Co. KG (Karlsruhe, Germany) as a positive control for direct-acting mutagens. The other reagents and solvents required for Ames/Salmonella assay were provided by Sigma–Aldrich® (St. Louis, MO, USA).
Molecular tissue profiling by MALDI imaging: recent progress and applications in cancer research
Published in Critical Reviews in Clinical Laboratory Sciences, 2021
Pey Yee Lee, Yeelon Yeoh, Nursyazwani Omar, Yuh-Fen Pung, Lay Cheng Lim, Teck Yew Low
Another critical aspect in MALDI imaging is the choice of matrix, in accordance with the type and mass range of the analytes of interest [27]. Sinapinic acid and 2,5-dihydroxybenzoic acid (DHB) are commonly used for proteins, whereas α-cyano-4-hydroxycinnamic acid (CHCA) is generally used for peptides. DHB matrix is also employed for carbohydrates and small molecules such as lipids and drugs (Table 2). In addition, one must consider the size and thickness of the matrix crystals, as they influence the spatial resolution and sensitivity of the analysis [54]. Matrix ions can also potentially mask analyte ions in the low mass region (<500 Da) and affect ionization efficiency, thereby interfering with the analyte signal [55]. Hence, an appropriate matrix should be used for the analysis of small molecules to avoid matrix interference. To analyze the diverse lipid classes, the selection of the MALDI matrix is particularly critical, as each matrix produces distinct lipid profiles and there is no single matrix that can provide molecular coverage for all lipid classes. In a recent study, a higher percentage of phosphatidylserines were detected with 9-aminoacridine (9AA) whereas a higher percentage of phosphatidylethanolamines were detected with 1,5‐diaminonaphthalene (DAN) [56]. Matrices that are commonly used for drug imaging are DHB, CHCA, 9AA, and DAN, but new matrices such as nanomaterials and different matrix combination have been tested to improve ionization efficiency and sensitivity [57,58].
Mass spectrometry-based phospholipid imaging: methods and findings
Published in Expert Review of Proteomics, 2020
Al Mamun, Ariful Islam, Fumihiro Eto, Tomohito Sato, Tomoaki Kahyo, Mitsutoshi Setou
– For MALDI, the tissue section is generally thaw-mounted on an indium tin oxide (ITO)-coated glass slide followed by a homogenous coating with a suitable matrix solution allowing the formation of co-crystals between the matrix molecules and the analytes. The matrix molecules must have the property of absorbing laser energy to aid in the ionization process. Various matrix compounds have been developed due to the fact that a single matrix does not work for all PLs. For instance, 2,5-Dihydroxybenzoic acid is commonly used to image PC molecules [50,51] in positive ion mode while 9-aminoacridine is used for imaging various PLs including PI, PG, PS, PA, and CL in negative ion mode [52]. Other matrices that have been used for the imaging of PLs include 2,5-dihydroxyacetophenone [53], α-cyano-4-hydroxycinnamic acid [50], graphene oxide [54], and 1,6-Diphenyl-1,3,5-hexatriene [55]. The matrix can be sprayed either manually (e.g., using artistic air brush) or automatically (e.g., using TM-SprayerTM manufactured by HTX Technologies, and ImagePrep manufactured by Bruker Daltonics Inc.) [56].