Novel alkylpolyaminoguanidines and alkylpolyaminobiguanides with potent antitrypanosomal activity.
A series of polyaminoguanidines and polyaminobiguanides were synthesized and evaluated as potential antitrypanosomal agents. These analogues inhibit trypanothione reductase (TR) with IC50 values as low as 0.95 microM, but do not inhibit the closely related human enzyme glutathione reductase (GR). The most effective analogues, 7a, 7b and 8d, inhibited parasitic growth in vitro with IC50 values of 0.18, 0.09 and 0.18 microM, respectively. These agents represent a promising new class of potential antitrypanosomal agents.
Bi
Xiangdong
X
Department of Pharmaceutical Sciences, Wayne State University, 259 Mack Ave, Detroit, MI 48202, USA.
Lopez
Christina
C
Bacchi
Cyrus J
CJ
Rattendi
Donna
D
Woster
Patrick M
PM
D000478:Alkylation; D000818:Animals; D000981:Antiprotozoal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D005980:Glutathione Reductase / Q000037:antagonists & inhibitors / Q000378:metabolism; D006146:Guanidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism; D013329:Structure-Activity Relationship; D014346:Trypanosoma brucei brucei / Q000187:drug effects* / Q000502:physiology
D000981:Antiprotozoal Agents; D006146:Guanidines; D009247:NADH, NADPH Oxidoreductases; C049608:trypanothione reductase; D005980:Glutathione Reductase; C004479:pimagedine