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Titolo:
PRECLINICAL PHARMACOLOGY OF ECTEINASCIDIN-729, A MARINE NATURAL PRODUCT WITH POTENT ANTITUMOR-ACTIVITY
Autore:
REID JM; WALKER DL; AMES MM;
Indirizzi:
MAYO CLIN & MAYO FDN,DEPT ONCOL,DIV DEV ONCOL RES,200 1ST ST SW ROCHESTER MN 55905 MAYO CLIN & MAYO FDN,DEPT ONCOL,DIV DEV ONCOL RES ROCHESTER MN 55905
Titolo Testata:
Cancer chemotherapy and pharmacology
fascicolo: 4, volume: 38, anno: 1996,
pagine: 329 - 334
SICI:
0344-5704(1996)38:4<329:PPOEAM>2.0.ZU;2-B
Fonte:
ISI
Lingua:
ENG
Soggetto:
CARIBBEAN TUNICATE; CRYSTAL-STRUCTURES; TURBINATA; BINDING;
Keywords:
ECTEINASCIDIN; MICE; PHARMACOKINETICS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
9
Recensione:
Indirizzi per estratti:
Citazione:
J.M. Reid et al., "PRECLINICAL PHARMACOLOGY OF ECTEINASCIDIN-729, A MARINE NATURAL PRODUCT WITH POTENT ANTITUMOR-ACTIVITY", Cancer chemotherapy and pharmacology, 38(4), 1996, pp. 329-334

Abstract

Ecteinascidins are marine natural products with potent antiproliferative activity under evaluation as chemotherapeutic agents by the National Cancer Institute. Ecteinascidins bind the minor groove of DNA and may form covalent adducts with DNA by binding the N-2 of guanine in a fashion similar to saframycin antibiotics. The most potent ecteinascidin is ET-729 with antitumor activity observed following administration of 3.8 and 10 mu g/kg to mice bearing P388 leukemia and B16 melanoma, respectively. A reverse-phase high-performance liquid chromatography (HPLC) assay and an L1210 cell bioassay were developed for ET-729 and utilized for stability and murine pharmacokinetic studies. HPLC analysis showed that ET-729 was stable in organic solvents,, mobile phase andacidic buffer (t(1/2) > 100 h). Stability was diminished under neutral and basic conditions (t(1/2) < 14 h). Following a 48 h incubation with L1210 cells in growth medium in the absence and presence of 2.5% murine plasma, the 50% growth inhibitory concentrations (IC50) of ET-729were 37 and 72 pM, respectively. Following intravenous administrationof ET-729 to male CD2F(1) mice, the disappearance of antiproliferative activity determined by the bioassay was described by a two-compartment open model. The mean values of the elimination half-life and plasmaclearance were 28 min and 39.7 ml/min per kg, respectively. Followingintraperitoneal administration, peak plasma concentrations of antiproliferative activity were: observed 6-15 min after injection and antiproliferative concentrations remained above 1 nM for longer than 1 h. Intraperitoneal bioavailability varied over a wide range (20-91%). Antiproliferative activity was detected in every urine sample following intravenous and intraperitoneal administration, but the total 48-h urinary recovery was less than 0.1%.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 10/07/20 alle ore 15:37:57