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Titolo:
Specific inhibition of Type II inosine monophosphate dehydrogenase activity of Tmolt(4) T cell human leukaemia cells by 3-methoxy and di-benzohydroxamic acids, maleic hydrazide and malonic acids
Autore:
Hall, IH; Barnes, BJ; Ward, ES; Wheaton, JR; Izydore, RA;
Indirizzi:
N Carolina Cent Univ, Sch Pharm, Div Med Chem & Nat Prod, Durham, NC 27707USA N Carolina Cent Univ Durham NC USA 27707 & Nat Prod, Durham, NC 27707USA
Titolo Testata:
JOURNAL OF PHARMACY AND PHARMACOLOGY
fascicolo: 5, volume: 53, anno: 2001,
pagine: 749 - 755
SICI:
0022-3573(200105)53:5<749:SIOTII>2.0.ZU;2-G
Fonte:
ISI
Lingua:
ENG
Soggetto:
5'-MONOPHOSPHATE DEHYDROGENASE; EXPRESSION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
16
Recensione:
Indirizzi per estratti:
Indirizzo: Izydore, RA N Carolina Cent Univ, Dept Chem, Durham, NC 27707 USA N Carolina Cent Univ Durham NC USA 27707 Durham, NC 27707 USA
Citazione:
I.H. Hall et al., "Specific inhibition of Type II inosine monophosphate dehydrogenase activity of Tmolt(4) T cell human leukaemia cells by 3-methoxy and di-benzohydroxamic acids, maleic hydrazide and malonic acids", J PHARM PHA, 53(5), 2001, pp. 749-755

Abstract

Small-molecular-weight benzohydroxamic and malonic acids and maleic hydrazide proved to be potent inhibitors of the activity of human Tmolt(4) leukaemia Type II IMP (inosine monophosphate) dehydrogenase (IMPDH) activity. They were competitive inhibitors with respect to IMPDH demonstrating K-i values in the range 2.57-41.3 muM. less than half the values of the IC50 (muM) for the inhibition of Type II IMPDH. The IC50 muM values positively correlated with the ability of each compound to inhibit crude IMPDH activity, de-novo purine and DNA syntheses and growth of the T leukaemia cell line. Compounds were not inhibitors of Type 1 IMPDH. Type I IMPDH predominates in normal resting cells compared with Type II which is found in rapidly proliferating cells. Discovery of agents which would selectivity target IMPDH found inproliferating cells should eliminate any antineoplastic therapeutic toxic effects in normal cells of the body.

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Documento generato il 27/11/20 alle ore 20:30:09