The effect of sulfonate leaving groups on the hypoxia-selective toxicity of nitro analogs of the duocarmycins.
Bioorg Med Chem
; 19(16): 4851-60, 2011 Aug 15.
Article
em En
| MEDLINE
| ID: mdl-21767954
ABSTRACT
A series of 3-substituted (5-nitro-2,3-dihydro-1H-benzo[e]indol-1-yl)methyl sulfonate (nitroCBI) prodrugs containing sulfonate leaving groups undergo hypoxia-selective metabolism to form potent DNA minor groove alkylating agents. They were evaluated (along with chloride leaving group analogs for comparison) for their cytotoxicity against cultures of SKOV3 and HT29 human tumor cell lines under both aerobic and hypoxic conditions. Sulfonates with neutral side chains (e.g., 5,6,7-trimethoxyindole; TMI) show consistently higher hypoxic cytotoxicity ratios (HCRs) (34-246) than the corresponding chloro analogs (2.8-3.1) in SKOV3 cells, but these trends do not hold for compounds with cationic or polar neutral side chains.
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Base de dados:
MEDLINE
Assunto principal:
Pró-Fármacos
/
Antineoplásicos Alquilantes
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Indóis
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Nitrocompostos
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article