Trypanocidal activity of dicationic compounds related to pentamidine

Eight dicationic compounds related to pentamidine were studied for trypanocidal activity in seven trypanosome isolates. In vitro studies revealed that diamidines are more potent than diimidazolines. For example, 2 (a diamidine) and 4 (a diimidazoline) inhibited the growth of KETRI 243 with IC 50 val...

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Bibliographic Details
Published in:European journal of medicinal chemistry 2001-06, Vol.36 (6), p.531-538
Main Authors: Donkor, Isaac O, Assefa, Haregewein, Rattendi, Donna, Lane, Schennella, Vargas, Marc, Goldberg, Burt, Bacchi, Cyrus
Format: Article
Language:English
Subjects:
Animals
Antibiotics. Antiinfectious agents. Antiparasitic agents
Antiparasitic agents
antitrypanosomal
Biological and medical sciences
Cations, Divalent - chemical synthesis
Cations, Divalent - chemistry
Cations, Divalent - pharmacology
Cations, Divalent - therapeutic use
Cattle
dicationic compounds
DNA - genetics
DNA - metabolism
Drug Design
Drug Evaluation, Preclinical
Female
Inhibitory Concentration 50
Magnetic Resonance Spectroscopy
Medical sciences
Mice
pentamidine
Pentamidine - analogs & derivatives
Pentamidine - chemical synthesis
Pentamidine - pharmacology
Pentamidine - therapeutic use
Pharmacology. Drug treatments
Structure-Activity Relationship
Thymus Gland
trypanocidal
Trypanocidal Agents - chemical synthesis
Trypanocidal Agents - chemistry
Trypanocidal Agents - pharmacology
Trypanocidal Agents - therapeutic use
Trypanosoma brucei brucei - drug effects
Trypanosoma brucei rhodesiense - drug effects
trypanosomiasis
Trypanosomiasis, African - drug therapy
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Summary:Eight dicationic compounds related to pentamidine were studied for trypanocidal activity in seven trypanosome isolates. In vitro studies revealed that diamidines are more potent than diimidazolines. For example, 2 (a diamidine) and 4 (a diimidazoline) inhibited the growth of KETRI 243 with IC 50 values of 2.3 and 900 nM, respectively. Introduction of polar groups into the linker decreased the effectiveness of the compounds against drug-resistant trypanosomes. In compounds with a 2-butene linker between the cationic groups, trans-isomers were more potent than cis-isomers. The cis- and trans-buteneamidines cured infection caused by Trypanosoma brucei brucei (EATRO Lab 110) and protected mice against infection by Trypanosoma brucei rhodesiense isolates, some of which are resistant to diamidines and melarsoprol.
ISSN:0223-5234
1768-3254
DOI:10.1016/S0223-5234(01)01250-8