Study of benzo[a]phenazine 7,12-dioxide as selective hypoxic cytotoxin-scaffold. Identification of aerobic-antitumoral activity through DNA fragmentation
Phenazine 5,10-dioxides are prodrugs for antitumor therapy that undergo hypoxic-selective bioreduction to form cytotoxic species. Here we investigate the expanded system benzo[a]phenazine 7,12-dioxides as selective hypoxic cytotoxin-scaffold. The clonogenic survival of V79 cells on aerobic and anaer...
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2010
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_09680896_v18_n12_p4433_Lavaggi http://hdl.handle.net/20.500.12110/paper_09680896_v18_n12_p4433_Lavaggi |
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paper:paper_09680896_v18_n12_p4433_Lavaggi2023-06-08T15:58:52Z Study of benzo[a]phenazine 7,12-dioxide as selective hypoxic cytotoxin-scaffold. Identification of aerobic-antitumoral activity through DNA fragmentation Benzo[a]phenazine 7,12-dioxides Bioreductive agents DNA fragmentation benzo[a]phenazine 7,12 dioxide cytotoxin unclassified drug antineoplastic agent phenazine derivative aerobic metabolism animal cell antineoplastic activity article cancer cell cell proliferation cell survival clonogenesis colon adenocarcinoma controlled study cytotoxicity DNA damage DNA fragmentation drug DNA interaction nonhuman animal CACO 2 cell line cell hypoxia cell line chemistry Colonic Neoplasms DNA fragmentation drug effects hamster human synthesis toxicity Animals Antineoplastic Agents Caco-2 Cells Cell Hypoxia Cell Line Colonic Neoplasms Cricetinae DNA Damage DNA Fragmentation Humans Phenazines Animals Antineoplastic Agents Caco-2 Cells Cell Hypoxia Cell Line Colonic Neoplasms Cricetinae DNA Damage DNA Fragmentation Humans Phenazines Phenazine 5,10-dioxides are prodrugs for antitumor therapy that undergo hypoxic-selective bioreduction to form cytotoxic species. Here we investigate the expanded system benzo[a]phenazine 7,12-dioxides as selective hypoxic cytotoxin-scaffold. The clonogenic survival of V79 cells on aerobic and anaerobic conditions, conduct us to study antiproliferative activity on Caco-2 tumoral cells in normoxia. Electrochemical, DNA-interaction and DNA-damage studies were performed to establish the mode of action. The results demonstrated the potential biological properties of the studied scaffold being derivatives 6-10 structural hits for further chemical-modifications to become into therapeutics for solid tumors. Compounds 6 and 8 with cytotoxicity against V79 cells in both conditions (aerobia and anaerobia) were also cytotoxic against Caco-2 tumoral cells in aerobiosis. © 2010 Elsevier Ltd. All rights reserved. 2010 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_09680896_v18_n12_p4433_Lavaggi http://hdl.handle.net/20.500.12110/paper_09680896_v18_n12_p4433_Lavaggi |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
Benzo[a]phenazine 7,12-dioxides Bioreductive agents DNA fragmentation benzo[a]phenazine 7,12 dioxide cytotoxin unclassified drug antineoplastic agent phenazine derivative aerobic metabolism animal cell antineoplastic activity article cancer cell cell proliferation cell survival clonogenesis colon adenocarcinoma controlled study cytotoxicity DNA damage DNA fragmentation drug DNA interaction nonhuman animal CACO 2 cell line cell hypoxia cell line chemistry Colonic Neoplasms DNA fragmentation drug effects hamster human synthesis toxicity Animals Antineoplastic Agents Caco-2 Cells Cell Hypoxia Cell Line Colonic Neoplasms Cricetinae DNA Damage DNA Fragmentation Humans Phenazines Animals Antineoplastic Agents Caco-2 Cells Cell Hypoxia Cell Line Colonic Neoplasms Cricetinae DNA Damage DNA Fragmentation Humans Phenazines |
| spellingShingle |
Benzo[a]phenazine 7,12-dioxides Bioreductive agents DNA fragmentation benzo[a]phenazine 7,12 dioxide cytotoxin unclassified drug antineoplastic agent phenazine derivative aerobic metabolism animal cell antineoplastic activity article cancer cell cell proliferation cell survival clonogenesis colon adenocarcinoma controlled study cytotoxicity DNA damage DNA fragmentation drug DNA interaction nonhuman animal CACO 2 cell line cell hypoxia cell line chemistry Colonic Neoplasms DNA fragmentation drug effects hamster human synthesis toxicity Animals Antineoplastic Agents Caco-2 Cells Cell Hypoxia Cell Line Colonic Neoplasms Cricetinae DNA Damage DNA Fragmentation Humans Phenazines Animals Antineoplastic Agents Caco-2 Cells Cell Hypoxia Cell Line Colonic Neoplasms Cricetinae DNA Damage DNA Fragmentation Humans Phenazines Study of benzo[a]phenazine 7,12-dioxide as selective hypoxic cytotoxin-scaffold. Identification of aerobic-antitumoral activity through DNA fragmentation |
| topic_facet |
Benzo[a]phenazine 7,12-dioxides Bioreductive agents DNA fragmentation benzo[a]phenazine 7,12 dioxide cytotoxin unclassified drug antineoplastic agent phenazine derivative aerobic metabolism animal cell antineoplastic activity article cancer cell cell proliferation cell survival clonogenesis colon adenocarcinoma controlled study cytotoxicity DNA damage DNA fragmentation drug DNA interaction nonhuman animal CACO 2 cell line cell hypoxia cell line chemistry Colonic Neoplasms DNA fragmentation drug effects hamster human synthesis toxicity Animals Antineoplastic Agents Caco-2 Cells Cell Hypoxia Cell Line Colonic Neoplasms Cricetinae DNA Damage DNA Fragmentation Humans Phenazines Animals Antineoplastic Agents Caco-2 Cells Cell Hypoxia Cell Line Colonic Neoplasms Cricetinae DNA Damage DNA Fragmentation Humans Phenazines |
| description |
Phenazine 5,10-dioxides are prodrugs for antitumor therapy that undergo hypoxic-selective bioreduction to form cytotoxic species. Here we investigate the expanded system benzo[a]phenazine 7,12-dioxides as selective hypoxic cytotoxin-scaffold. The clonogenic survival of V79 cells on aerobic and anaerobic conditions, conduct us to study antiproliferative activity on Caco-2 tumoral cells in normoxia. Electrochemical, DNA-interaction and DNA-damage studies were performed to establish the mode of action. The results demonstrated the potential biological properties of the studied scaffold being derivatives 6-10 structural hits for further chemical-modifications to become into therapeutics for solid tumors. Compounds 6 and 8 with cytotoxicity against V79 cells in both conditions (aerobia and anaerobia) were also cytotoxic against Caco-2 tumoral cells in aerobiosis. © 2010 Elsevier Ltd. All rights reserved. |
| title |
Study of benzo[a]phenazine 7,12-dioxide as selective hypoxic cytotoxin-scaffold. Identification of aerobic-antitumoral activity through DNA fragmentation |
| title_short |
Study of benzo[a]phenazine 7,12-dioxide as selective hypoxic cytotoxin-scaffold. Identification of aerobic-antitumoral activity through DNA fragmentation |
| title_full |
Study of benzo[a]phenazine 7,12-dioxide as selective hypoxic cytotoxin-scaffold. Identification of aerobic-antitumoral activity through DNA fragmentation |
| title_fullStr |
Study of benzo[a]phenazine 7,12-dioxide as selective hypoxic cytotoxin-scaffold. Identification of aerobic-antitumoral activity through DNA fragmentation |
| title_full_unstemmed |
Study of benzo[a]phenazine 7,12-dioxide as selective hypoxic cytotoxin-scaffold. Identification of aerobic-antitumoral activity through DNA fragmentation |
| title_sort |
study of benzo[a]phenazine 7,12-dioxide as selective hypoxic cytotoxin-scaffold. identification of aerobic-antitumoral activity through dna fragmentation |
| publishDate |
2010 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_09680896_v18_n12_p4433_Lavaggi http://hdl.handle.net/20.500.12110/paper_09680896_v18_n12_p4433_Lavaggi |
| _version_ |
1768541571195600896 |