Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
STUDIES ON THE TOXICITY OF ANALOGS OF DAPSONE IN-VITRO USING RAT, HUMAN AND HETEROLOGOUSLY EXPRESSED METABOLIZING SYSTEMS
Autore:
COLEMAN MD; SMITH SN; KELLY DE; KELLY SL; SEYDEL JK;
Indirizzi:
ASTON UNIV,DEPT PHARMACEUT SCI,MECHANISMS DRUG TOX GRP,ASTON TRIANGLEBIRMINGHAM B4 7ET W MIDLANDS ENGLAND UNIV SHEFFIELD,KREBS INST BIOMOLEC RES,DEPT MOL BIOL & BIOTECHNOL SHEFFIELD S10 2TN S YORKSHIRE ENGLAND FORSCHUNGSZENTRUM BORSTEL,ZENTRUM MED & BIOWISSENSCH D-23845 BORSTEL GERMANY
Titolo Testata:
Journal of Pharmacy and Pharmacology
fascicolo: 9, volume: 48, anno: 1996,
pagine: 945 - 950
SICI:
0022-3573(1996)48:9<945:SOTTOA>2.0.ZU;2-9
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN CYTOCHROME-P450 3A4; HUMAN-LIVER-MICROSOMES; N-HYDROXYLATION; METHEMOGLOBIN FORMATION; HEMATOLOGICAL TOXICITY; HUMAN ERYTHROCYTES; ENZYMES; INVITRO; SUSCEPTIBILITY; CIMETIDINE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
39
Recensione:
Indirizzi per estratti:
Citazione:
M.D. Coleman et al., "STUDIES ON THE TOXICITY OF ANALOGS OF DAPSONE IN-VITRO USING RAT, HUMAN AND HETEROLOGOUSLY EXPRESSED METABOLIZING SYSTEMS", Journal of Pharmacy and Pharmacology, 48(9), 1996, pp. 945-950

Abstract

Three metabolizing systems (rat, heterologously expressed CYP3A4 and human liver) were used to evaluate 12 analogues of dapsone (4,4'diaminodiphenylsulphone) in-vitro. Methaemoglobin formation in a two-compartment and cytotoxicity in a single-compartment model were studied usinghuman erythrocytes and neutrophils, respectively, as target cells. Inthe two-compartment system using rat microsomes as a generating system and methaemoglobin as an endpoint, the least potent methaemoglobin formers tested were the 2-methyl-4-propylamino (AXDD14), 2-hydroxy-4-4'-amino (ABDD5) derivatives and a sulphone/trimethoprim derivative (K-130). Dapsone itself, a 2-methoxy-4-ethylamino (W10) and a 2-hydroxyl-4-ethylamino compound (ABDD39) were the most toxic. In the single-compartment cytotoxicity test using rat microsomes, AXDD14 was again among the least toxic, as was a 2-methyl 4-cyclopentyl derivative (AXDD17) and surprisingly ABDD39. The most cytotoxic compounds again included dapsone itself as well as two 2-trifluoromethyl derivatives. The only significant methaemoglobin formation and cytotoxicity shown with the heterologously expressed human CYP3A4 was with AXDD14, which was extensively activated. Interestingly, metabolism of dapsone was low using the expressed CYP3A4. In the two-compartment system using human liver microsomes, AXDD14, K-130 and ABDD5 were oxidized to a significantly lesser extent compared with dapsone and these preliminary findings indicatethat future development of these compounds may be worthwhile.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 18/01/20 alle ore 13:09:50