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Titolo:
REVERSAL OF MULTIDRUG-RESISTANCE BY DERIVATIVES OF ACRIVASTINE - A STUDY OF STRUCTURE-ACTIVITY-RELATIONSHIPS OF P-GLYCOPROTEIN INHIBITORS IN-VITRO AND IN-VIVO
Autore:
CHRISTENSEN JG; PARKS LG; MCNUTT RW; LEBLANC GA;
Indirizzi:
N CAROLINA STATE UNIV,DEPT TOXICOL RALEIGH NC 27695 N CAROLINA STATE UNIV,DEPT TOXICOL RALEIGH NC 27695 WELLCOME RES LABS RES TRIANGLE PK NC 27709
Titolo Testata:
Oncology Reports
fascicolo: 6, volume: 4, anno: 1997,
pagine: 1353 - 1360
SICI:
1021-335X(1997)4:6<1353:ROMBDO>2.0.ZU;2-E
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN-LEUKEMIC-CELLS; GENE; VINCRISTINE; EXPRESSION; DOXORUBICIN; SENSITIVITY; COLCHICINE; ADRIAMYCIN; INVITRO; LINES;
Keywords:
MULTIDRUG RESISTANCE; ACRIVASTINE; BENZYL PIPERAZINE; P-GLYCOPROTEIN; CANCER CHEMOTHERAPY; IN VIVO; STRUCTURE-ACTIVITY RELATIONSHIPS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
38
Recensione:
Indirizzi per estratti:
Citazione:
J.G. Christensen et al., "REVERSAL OF MULTIDRUG-RESISTANCE BY DERIVATIVES OF ACRIVASTINE - A STUDY OF STRUCTURE-ACTIVITY-RELATIONSHIPS OF P-GLYCOPROTEIN INHIBITORS IN-VITRO AND IN-VIVO", Oncology Reports, 4(6), 1997, pp. 1353-1360

Abstract

A major obstacle to successful cancer chemotherapy is the developmentof multidrug resistance (MDR) characterized by the overexpression of the drug transporter P-glycoprotein and the enhanced cellular efflux of many anticancer drugs. The identification and use of agents that reverse the MDR phenotype or drug-resistant tumors could provide an adjuvant to conventional cancer chemotherapy that would significantly enhance treatment efficacy. Several derivatives of acrivastine and a structurally-related benzyl piperazine were used in the present study to establish the utility of structure-activity and in vitro analyses to identify compounds that are effective at sensitizing MDR tumors in vivo. Of the seven compounds evaluated, 5 were identified by structure-activity analyses as inhibitors of P-glycoprotein, 1 was identified as a possible inhibitor, and 1 was deemed a non-interactor. In vitro analyses indicated that all seven compounds could inhibit P-glycoprotein; however, the compound identified by structure-activity analyses as a non-interactor was least potent. In vivo experimentation revealed that the more potent P-glycoprotein inhibitors, as determined by either structure-activity analyses or in vitro testing, also sensitized multidrug-resistant tumor masses implanted into athymic nude mice to treatment withvinblastine; though, efficacy was limited by host toxicity. Results from this study corroborate previously-established relationships between chemical structure and P-glycoprotein inhibition. Results further demonstrate that P-glycoprotein inhibitory potency, as established by structure-activity or in vitro analyses, provides insight into the ability of the agent to sensitize drug-resistant tumors in vivo.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/07/20 alle ore 11:28:20