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Bioorg Med Chem ; 14(23): 8066-72, 2006 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-16919464

RESUMO

Biscoumarin derivatives 1-27 were tested for their inhibition of snake venom and human nucleotide pyrophosphatase phosphodiesterase-1 enzymes. Lineweaver-Burk and Dixon plots and their secondary replots showed that these compounds are pure non-competitive inhibitors of both the enzymes. Ki and IC50 values of biscoumarins were found to be in the range of 50 to 1000 and 164 to > 1000 microM, respectively, against human recombinant phosphodiesterase 1 enzyme and 8.0 to 1150 and 9.44 to > 1000 microM, respectively, against snake venom phosphodiesterase. Compounds 1, 3, 4, 6, 7, 17, 26, and 30 were found to be non-competitive and non-cytotoxic upto a concentration of 200 microg/mL as evident by less than 10% cell death after 3 h of incubation.


Assuntos
Cumarínicos/farmacologia , Inibidores Enzimáticos/síntese química , Fosfodiesterase I/antagonistas & inibidores , Pirofosfatases/antagonistas & inibidores , Morte Celular/efeitos dos fármacos , Cumarínicos/síntese química , Avaliação Pré-Clínica de Medicamentos , Inibidores Enzimáticos/farmacologia , Humanos , Concentração Inibidora 50 , Cinética , Diester Fosfórico Hidrolases , Venenos de Serpentes/enzimologia
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