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Titolo:
Synthesis and antitumor activity of duocarmycin derivatives: Modification at C-8 position of A-ring pyrrole compounds bearing the simplified DNA-binding groups
Autore:
Amishiro, N; Nagamura, S; Murakata, C; Okamoto, A; Kobayashi, E; Asada, M; Gomi, K; Tamaoki, T; Okabe, M; Yamaguchi, N; Yamaguchi, K; Saito, H;
Indirizzi:
Kyowa Hakko Kogyo Co Ltd, Pharmaceut Res Inst, Shizuoka 4118731, Japan Kyowa Hakko Kogyo Co Ltd Shizuoka Japan 4118731 Shizuoka 4118731, Japan
Titolo Testata:
BIOORGANIC & MEDICINAL CHEMISTRY
fascicolo: 2, volume: 8, anno: 2000,
pagine: 381 - 391
SICI:
0968-0896(200002)8:2<381:SAAAOD>2.0.ZU;2-X
Fonte:
ISI
Lingua:
ENG
Soggetto:
PYRINDAMYCIN ALKYLATION SUBUNIT; WAGNER-MEERWEIN REARRANGEMENT; LUNG-CANCER CELLS; STREPTOMYCES SP; COMMON PHARMACOPHORE; SEQUENCE SPECIFICITY; BIOLOGICAL-ACTIVITY; CC-1065 NSC-298223; ANTIBIOTIC CC-1065; CARBOXYL ESTERASE;
Keywords:
antibiotics; antitumor compounds; DNA; natural products; prodrug;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
50
Recensione:
Indirizzi per estratti:
Indirizzo: Amishiro, N Kyowa Hakko Kogyo Co Ltd, Pharmaceut Res Inst, 1188 Shimotogari, Shizuoka 4118731, Japan Kyowa Hakko Kogyo Co Ltd 1188 Shimotogari Shizuoka Japan 4118731
Citazione:
N. Amishiro et al., "Synthesis and antitumor activity of duocarmycin derivatives: Modification at C-8 position of A-ring pyrrole compounds bearing the simplified DNA-binding groups", BIO MED CH, 8(2), 2000, pp. 381-391

Abstract

A series of the 8-O-substituted A-ring pyrrole derivatives of duocarmycin bearing the simplified DNA-binding moieties such as cinnamoyl or heteroarylacryloyl groups were synthesized, and evaluated for in vitro anticellular activity against HeLa S-3 cells and in vivo antitumor activity against murine sarcoma 180 in mice. In addition, the stability of the 8-O-substituted analogues in aqueous solution and the conversion to their active form (cyclopropane compound) from the 8-O-substituted analogues in mice or human serum were examined. The 8-O-substituted A-ring pyrrole derivatives bearing the simplified DNA-binding moieties showed remarkably potent in vivo antitumor activity and low peripheral blood toxicity compared with the 8-O-substitutedA-ring pyrrole derivatives having the trimethoxyindole skeleton in segment-B (Seg-B), which were equal to 8-O-[(N-methylpiperazinyl)carbonyl] derivatives of 4'-methoxycinnamates and 4'-methoxy-beta-heteroarylacrylates. Moreover, among 8-O-substituted analogues, several compounds can be chemically or enzymatically converted to their active form in human serum. This result indicated that new 8-O-substituted derivatives were different prodrugs fromKW-2189 and 8-O-substituted analogues being the same type of prodrug as KW-21S9. (C) 2000 Elsevier Science Ltd. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/12/20 alle ore 12:00:37