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Titolo:
Cell-based screen for antimitotic agents and identification of analogues of rhizoxin, eleutherobin, and paclitaxel in natural extracts
Autore:
Roberge, M; Cinel, B; Anderson, HJ; Lim, L; Jiang, XX; Xu, L; Bigg, CM; Kelly, MT; Andersen, RJ;
Indirizzi:
Univ British Columbia, Dept Biochem & Mol Biol, Vancouver, BC V6T 1Z3, Canada Univ British Columbia Vancouver BC Canada V6T 1Z3 ver, BC V6T 1Z3, Canada Univ British Columbia, Dept Chem, Vancouver, BC V6T 1Z1, Canada Univ British Columbia Vancouver BC Canada V6T 1Z1 ver, BC V6T 1Z1, Canada Univ British Columbia, Dept Oceanog, Vancouver, BC V6T 1Z1, Canada Univ British Columbia Vancouver BC Canada V6T 1Z1 ver, BC V6T 1Z1, Canada SeaTek Marine Biotechnol Inc, Surrey, BC V4A 7M4, Canada SeaTek Marine Biotechnol Inc Surrey BC Canada V4A 7M4 BC V4A 7M4, Canada
Titolo Testata:
CANCER RESEARCH
fascicolo: 18, volume: 60, anno: 2000,
pagine: 5052 - 5058
SICI:
0008-5472(20000915)60:18<5052:CSFAAA>2.0.ZU;2-T
Fonte:
ISI
Lingua:
ENG
Soggetto:
MACROCYCLIC LACTONE ANTIBIOTICS; MICROTUBULE-STABILIZING AGENTS; TUBULIN POLYMERIZATION; RHIZOPUS-CHINENSIS; MITOTIC SPINDLES; ANTITUMOR AGENT; TAXOL; BINDING; INHIBITION; FUNGUS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
55
Recensione:
Indirizzi per estratti:
Indirizzo: Roberge, M Univ British Columbia, Dept Biochem & Mol Biol, 2146 Hlth Sci Mall, Vancouver, BC V6T 1Z3, Canada Univ British Columbia 2146 Hlth Sci MallVancouver BC Canada V6T 1Z3
Citazione:
M. Roberge et al., "Cell-based screen for antimitotic agents and identification of analogues of rhizoxin, eleutherobin, and paclitaxel in natural extracts", CANCER RES, 60(18), 2000, pp. 5052-5058

Abstract

We describe a cell-based assay for antimitotic compounds that is suitable for drug discovery and for quantitative determination of antimitotic activity, In the assay, cells arrested in mitosis as a result of exposure to antimitotic agents in pure form or in crude natural extracts are detected by ELISA using the monoclonal antibody TG-3, The assay was used to screen >24,000 extracts of marine microorganisms and invertebrates and terrestrial plants and to guide the purification of active compounds from 5 of 119 positive extracts. A new rhizoxin analogue was found in a Pseudomonas species, six new eleutherobin analogues were identified from the octocoral Erythropodium caribaeorum, and two paclitaxel analogues were found in the stem bark of the tree Ilex macrophylla. The assay was also used for quantitative comparison of the antimitotic activity of different analogues. It revealed the importance of the C-11 to C-13 segment of the diterpene core of eleutherobin forits antimitotic activity. The identification of antimitotic compounds in very low abundance and their high (0.5%) occurrence in natural extracts indicates that drug discovery efforts using this cell-based assay may lead to the identification of structurally novel antimitotic agents.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 23/09/20 alle ore 15:51:14