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Titolo:
Does the antitumor cyclopropylpyrroloindole antibiotic CC-1065 cross-link DNA in tumor cells?
Autore:
Skladanowski, A; Koba, M; Konopa, J;
Indirizzi:
Univ Gdansk, Dept Pharmaceut Technol & Biochem, PL-80952 Gdansk, Poland Univ Gdansk Gdansk Poland PL-80952 ol & Biochem, PL-80952 Gdansk, Poland
Titolo Testata:
BIOCHEMICAL PHARMACOLOGY
fascicolo: 1, volume: 61, anno: 2001,
pagine: 67 - 72
SICI:
0006-2952(20010101)61:1<67:DTACAC>2.0.ZU;2-1
Fonte:
ISI
Lingua:
ENG
Soggetto:
SEQUENCE SPECIFICITY; ANALOGS; BIZELESIN; INDUCTION; U-77,779; ASSAY; SITE;
Keywords:
CC-1065; interstrand DNA cross-links; cytotoxicity; metabolic activation;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
26
Recensione:
Indirizzi per estratti:
Indirizzo: Konopa, J Univ Gdansk, Dept Pharmaceut Technol & Biochem, Narutowicza St 11, PL-80952 Gdansk, Poland Univ Gdansk Narutowicza St 11 Gdansk Poland PL-80952 sk, Poland
Citazione:
A. Skladanowski et al., "Does the antitumor cyclopropylpyrroloindole antibiotic CC-1065 cross-link DNA in tumor cells?", BIOCH PHARM, 61(1), 2001, pp. 67-72

Abstract

We have found that a cyclopropylpyrroloindole antibiotic, compound CC-1065(benzo[1,2-b:4,3-b']dipyrrole-3(2H)-carboxamide, 7-[[1,6-dihydro-4-hydroxy-5-methoxy-7-[(4,5,8,8a-tetrahydro-7-methyl-4-oxocyclopropan[c]pyrrolo[3,2-e]indol-2(1H)-yl)carbonyl]benzo[1,2-b: 4,3-b']dipyrrol-3(2H)-yl]-carbonyl]-1,6-dihydro-4-hydroxy-5-methoxy, (7bR,8aS)), forms interstrand DNA cross-links of an apparently covalent nature in HeLa S-3 cells. This compound induced interstrand cross-links at concentrations ranging from 0.1 to 1 nM/3 hr in whole cells, but these cross-links were absent or marginally low when the drug was added to cell lysates with inactivated cellular enzymes or isolated nuclei, which suggests that metabolic activation of the drug is a necessary step for DNA cross-linking to occur. In contrast, an analog of CC-1065, Bizelesin, which forms DNA-DNA cross-links by direct alkylation, induced interstrand DNA cross-links in both whole cells and in cell lysates. Interestingly, a demethoxy analog of CC-1065. Adozelesin, did not induce DNA cross-links under the same conditions. CC-1065 was found to be extremely potentin terms of concentrations required to cross-link DNA of tumor cells, and this may be related to its remarkable cytotoxic activity. (C) 2000 ElsevierScience Inc. All lights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 02/04/20 alle ore 00:03:19