CBI NITRO PDF

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Hypoxia represents an important therapeutic target in tumors because of the resistance of hypoxic cells to radiotherapy and chemotherapy and because it is more severe in many tumors than in normal tissues.

Here, we describe a class of prodrugs, nitro-chloromethylindolines, which undergo hypoxia-selective activation by endogenous nitroreductases in tumor cells to form the corresponding amino compounds.

The latter are chemically related to the cyclopropylindoline antitumor antibiotics and they share the same properties of sequence-selective DNA minor groove alkylation and high cytotoxic potency. Selective alkylation of adenine N3 in calf thymus DNA by an amino-CBI was shown by characterization of the thermal depurination product; the same adduct was shown in hypoxic RIF-1 cells exposed to the corresponding nitro-CBI prodrug under hypoxic but not oxic conditions.

The amino metabolite generated from a nitro-CBI by cells expressing Escherichia coli nfsB nitroreductase in multicellular layer cultures was shown to elicit bystander killing of surrounding cells. Nitro-CBIs are novel lead hypoxia-activated prodrugs that represent the first examples of hypoxia-selective generation of potent DNA minor groove alkylating agents. This site needs JavaScript to work properly. Please enable it to take advantage of the complete set of features!

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Green LK, et al. Mol Cancer. Hypoxia-activated prodrugs: substituent effects on the properties of nitro seco-1,2,9,9a-tetrahydrocyclopropa[c]benz[e]indolone nitroCBI prodrugs of DNA minor groove alkylating agents. Tercel M, et al. J Med Chem. PMID: Synthesis and evaluation of nitroheterocyclic carbamate prodrugs for use with nitroreductase-mediated gene-directed enzyme prodrug therapy.

Hay MP, et al. Bioreductive prodrugs as cancer therapeutics: targeting tumor hypoxia. Guise CP, et al. Chin J Cancer. Epub Jul DNA minor groove alkylating agents. Denny WA. Curr Med Chem.

PMID: Review. Show more similar articles See all similar articles. Hypoxia-targeted drug delivery. Sharma A , et al. Chem Soc Rev. Cancers Basel. Publication types Research Support, Non-U. Gov't Actions. Animals Actions.

Cell Culture Techniques Actions. Cell Line, Tumor Actions. Humans Actions. Inhibitory Concentration 50 Actions. Mice Actions. Tumor Stem Cell Assay Actions. Xenograft Model Antitumor Assays Actions.

Substances Alkylating Agents Actions. Antineoplastic Agents Actions. DNA Adducts Actions. Indoles Actions. Prodrugs Actions. DNA Actions. Adenine Actions. Full-text links [x] HighWire. Copy Download.

DISCURSO A DIOGNETO PDF

Synthesis, Cytotoxicity and Antifungal Activity of 5-nitro-thiophene-thiosemicarbazones Derivatives

In the present work, twelve N-substituted 2- 5-nitro-thiophene -thiosemicarbazones derivatives L were synthesized, characterized and their in vitro cytotoxic and antifungal activities were evaluated against Candida sp. The probable mechanisms of action have been investigated by sorbitol and ergosterol assays. Additionally, ultrastructural study by Scanning Electron Microscopy was performed with the L10 compound. The results showed that all strains were more sensitive to the compound L10 except Candida tropicalis URM Concerning the study of the possible mechanism of action, the compounds were not able to bind to ergosterol in the membrane, do not act by inhibiting the synthesis of fungal cell wall sorbitol assay. However, the Scanning Electron Microscopy - SEM analysis shows significant morphological changes in shape, size, number of cells and hyphae, and cell wall indicating a possible mechanism of action by inhibition of enzymes related to the ergosterol biosynthesis pathway.

GOST 10704 PDF

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