PMID: 9662031Jul 14, 1998Paper

Arrest of Trypanosoma brucei rhodesiense and T. brucei brucei in the S-phase of the cell cycle by (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine ((S)-HPMPA)

Molecular and Biochemical Parasitology
R KaminskyA Holý

Abstract

African trypanosomes are incapable of purine de novo synthesis. They use salvage pathways to meet their purine requirements. Therefore, purine analogues appear as potential candidates to interfere in trypanosome metabolism. The acyclic adenosine analogue (S)-9-(-3-hydroxy-2-phosphonylmethoxypropyl)adenine ((S)-HPMPA) expressed antitrypanosomal activity in vitro and vivo. When exposed to 20 microM (S)-HPMPA, trypanosomes were arrested in the S-phase of the cell cycle and were unable to enter G2-phase. Thymidine uptake and incorporation was inhibited almost completely. Only nuclear DNA replication was inhibited, while mitochondrial DNA replication and kinetoplast division was not inhibited. The antitrypanosomal effect was reversible when cells were exposed for 12 h. As a control, aphidicolin arrested trypanosomes in the G1-phase of the cell cycle at a concentration of 30 microM. At 20 microM (S)-HPMPA, glycolysis was not effected, while leucine and adenine uptake were reduced with prolonged exposure.

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Citations

Jan 19, 2000·Parasitology Today·S V Barrett, M P Barrett
Dec 20, 2000·Antimicrobial Agents and Chemotherapy·O KayserK Siems
Feb 26, 2008·Eukaryotic Cell·Marianne K PoxleitnerW Zacheus Cande
Dec 5, 2006·Proceedings of the National Academy of Sciences of the United States of America·Sunil LaxmanJoseph A Beavo

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