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Titolo:
MONOFUNCTIONAL AND DIFUNCTIONAL NITROGEN-MUSTARD ANALOGS OF THE DNA MINOR-GROOVE BINDER PIBENZIMOL - SYNTHESIS, CYTOTOXICITY AND INTERACTION WITH DNA
Autore:
SMAILL JB; FAN JY; PAPA PV; OCONNOR CJ; DENNY WA;
Indirizzi:
UNIV AUCKLAND,SCH MED,CANC RES LAB,PRIVATE BAG 92019 AUCKLAND NEW ZEALAND UNIV AUCKLAND,SCH MED,CANC RES LAB AUCKLAND NEW ZEALAND UNIV AUCKLAND,DEPT CHEM AUCKLAND NEW ZEALAND
Titolo Testata:
Anti-cancer drug design
fascicolo: 3, volume: 13, anno: 1998,
pagine: 221 - 242
SICI:
0266-9536(1998)13:3<221:MADNAO>2.0.ZU;2-Q
Fonte:
ISI
Lingua:
ENG
Soggetto:
DIRECTED ALKYLATING-AGENTS; ANTITUMOR-ACTIVITY; BIOLOGICAL EVALUATION; ANILINE MUSTARDS; CROSS-LINKING; DISTAMYCIN; HOECHST-33258; DERIVATIVES; DESIGN;
Keywords:
ANALOGS; MINOR GROOVE BINDING; NITROGEN MUSTARD; PIBENZIMOL;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
31
Recensione:
Indirizzi per estratti:
Citazione:
J.B. Smaill et al., "MONOFUNCTIONAL AND DIFUNCTIONAL NITROGEN-MUSTARD ANALOGS OF THE DNA MINOR-GROOVE BINDER PIBENZIMOL - SYNTHESIS, CYTOTOXICITY AND INTERACTION WITH DNA", Anti-cancer drug design, 13(3), 1998, pp. 221-242

Abstract

Two series of mono-and difunctional aniline mustards linked to a bisbenzimidazole minor groove binder have been prepared using a new method(polyphosphate ester-mediated direct coupling of appropriate mustard acids with a preformed advanced phenylenediamine intermediate). As thelinker chain attaching the mustard was lengthened the binding site size of the compounds to calf thymus DNA remained essentially constant at 2.6 nucleotides, but reversible binding strength declined by a factor of 2. Analogues with longer linker chains alkylated DNA much more rapidly than those with shorter chains, consistent with the electronic factors. The short chain analogues also failed to alkylate a 120 bp HindIII to Bg/II fragment of the gpt gene, as measured by gel electrophoresis cleavage assays. The longer chain analogues (both mono- and difunctional mustards) showed patterns of DNA alkylation that varied with chain length. In particular, while most compounds showed substantial N7alkylation at many guanine residues, the analogue with a (CH2)(3) linker chain showed strong alkylation at adenine sites in poly-AT regions. For the longer chain analogues, the bifunctional mustards were substantially (10- to 20-fold) more cytotoxic than the corresponding monofunctional analogues.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 26/11/20 alle ore 11:34:33