TY - JOUR
T1 - Benzofuranyl 3,5-bis-polyamine derivatives as time-dependent inhibitors of trypanothione reductase
AU - Hamilton, Chris J.
AU - Saravanamuthu, Ahilan
AU - Fairlamb, Alan H.
AU - Eggleston, Ian M.
PY - 2003/8/15
Y1 - 2003/8/15
N2 - The synthesis and evaluation of 3,5-disubstituted benzofuran derivatives as time-dependent inhibitors of the protozoan oxidoreductase trypanothione reductase are reported. These molecules were designed as simplified mimetics of the naturally occurring spermidine-bridged macrocyclic alkaloid lunarine 1, a known time-dependent inhibitor of trypanothione reductase. In this series of compounds the bis-polyaminoacrylamide derivatives 2-4 were all shown to be competitive inhibitors, but only the bis-4-methyl-piperazin-1-yl-propylacrylamide derivative 4 displayed time-dependent activity. The kinetics of time dependent inactivation of trypanothione reductase by 1 and 4 have been determined and are compared and discussed herein.
AB - The synthesis and evaluation of 3,5-disubstituted benzofuran derivatives as time-dependent inhibitors of the protozoan oxidoreductase trypanothione reductase are reported. These molecules were designed as simplified mimetics of the naturally occurring spermidine-bridged macrocyclic alkaloid lunarine 1, a known time-dependent inhibitor of trypanothione reductase. In this series of compounds the bis-polyaminoacrylamide derivatives 2-4 were all shown to be competitive inhibitors, but only the bis-4-methyl-piperazin-1-yl-propylacrylamide derivative 4 displayed time-dependent activity. The kinetics of time dependent inactivation of trypanothione reductase by 1 and 4 have been determined and are compared and discussed herein.
UR - http://www.scopus.com/inward/record.url?scp=0013356477&partnerID=8YFLogxK
U2 - 10.1016/S0968-0896(03)00344-4
DO - 10.1016/S0968-0896(03)00344-4
M3 - Article
C2 - 12901914
AN - SCOPUS:0013356477
VL - 11
SP - 3683
EP - 3693
JO - Bioorganic & Medicinal Chemistry
JF - Bioorganic & Medicinal Chemistry
SN - 0968-0896
IS - 17
ER -