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Titolo:
Design, synthesis, and evaluation of inhibitors of trypanosomal and leishmanial dihydrofolate reductase
Autore:
Chowdhury, SF; Villamor, VB; Guerrero, RH; Leal, I; Brun, R; Croft, SL; Goodman, JM; Maes, L; Ruiz-Perez, LM; Pacanowska, DG; Gilbert, IH;
Indirizzi:
Cardiff Univ, Welsh Sch Pharm, Cardiff CF10 3XF, S Glam, Wales Cardiff Univ Cardiff S Glam Wales CF10 3XF ardiff CF10 3XF, S Glam, Wales CSIC, Inst Parasitol & Biomed, Granada 18001, Spain CSIC Granada Spain 18001 , Inst Parasitol & Biomed, Granada 18001, Spain Swiss Trop Inst, CH-4002 Basel, Switzerland Swiss Trop Inst Basel Switzerland CH-4002 st, CH-4002 Basel, Switzerland Univ London London Sch Hyg & Trop Med, London WC1E 7HT, England Univ London London Sch Hyg & Trop Med London England WC1E 7HT T, England Univ Cambridge, Dept Chem, Cambridge CB2 1EW, England Univ Cambridge Cambridge England CB2 1EW hem, Cambridge CB2 1EW, England Tibotec NV, B-2800 Mechelen, Belgium Tibotec NV Mechelen Belgium B-2800Tibotec NV, B-2800 Mechelen, Belgium
Titolo Testata:
JOURNAL OF MEDICINAL CHEMISTRY
fascicolo: 21, volume: 42, anno: 1999,
pagine: 4300 - 4312
SICI:
0022-2623(19991021)42:21<4300:DSAEOI>2.0.ZU;2-#
Fonte:
ISI
Lingua:
ENG
Soggetto:
GROWTH; METHOTREXATE; RHODESIENSE; GAMBIENSE; BRUCEI;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
17
Recensione:
Indirizzi per estratti:
Indirizzo: Gilbert, IH Cardiff Univ, Welsh Sch Pharm, Redwood Bldg,King Edward VII Ave, Cardiff CF10 3XF, S Glam, Wales Cardiff Univ Redwood Bldg,King Edward VII Ave Cardiff S Glam Wales CF10 3XF
Citazione:
S.F. Chowdhury et al., "Design, synthesis, and evaluation of inhibitors of trypanosomal and leishmanial dihydrofolate reductase", J MED CHEM, 42(21), 1999, pp. 4300-4312

Abstract

This paper concerns the design, synthesis, and evaluation of inhibitors ofleishmanial and trypanosomal dihydrofolate reductase. Initially study was made of the structures of the leishmanial and human enzyme active sites to see if there were significant differences which could be exploited for selective drug design. Then a series of compounds were synthesized based on 5-benzyl-2,4-diaminopyrimidines. These compounds were assayed against the protozoan and human enzymes and showed selectivity for the protozoan enzymes. The structural data was then used to rationalize the enzyme assay data. Compounds were also tested against the clinically relevant forms of the intact parasite. Activity was seen against the trypanosomes for a number of compounds. The compounds were in general less active against Leishmania. This latter result may be due to uptake problems. Two of the compounds also showed some in vivo activity in a model of African trypanosomiasis.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 26/01/21 alle ore 03:55:06