1996 Fiscal Year Final Research Report Summary
Establishment of an in vitro screening system for anti-Trypanosoma cruzi agents
| Project/Area Number |
07557211
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 試験 |
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| Research Field |
寄生虫学(含医用動物学)
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| Research Institution | Juntendo University |
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Principal Investigator |
AOKI Takashi Parasitology, Juntendo Univ.Sch.Med.Prof., 医学部, 教授 (20053283)
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| Co-Investigator(Kenkyū-buntansha) |
SHIMOGAWARA Reiko Parasitology, Juntendo Univ.Sch.Med.Asoc.Res., 医学部, 助手 (50146776)
SHIMADA Junko Parasitology, Juntendo Univ.Sch.Med.Lect., 医学部, 講師 (20211964)
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| Project Period (FY) |
1995 – 1996
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| Keywords | anti-trypanosomal drugs / Trypanosoma cruzi / Changas' disease / drug-screening system / AZT / Calcium antagonist / synthetic peptides / natural plant drugs |
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| Research Abstract |
The purpose of this study was to establish an in vitro screening system that enables us to search for potent anti-Trypanosoma cruzi agents. We have succeeded in establishing an in vitro culture system using mammalian host cells (HeLa) infected with T.cruzi in which the time course of parasite growth is determined quantitatively. We adopted this system for the screening of anti-T.cruzi agents that would ideally prove to be effective against trypanosomes with no toxicity to the host cell. Of the purine analogs tested, allopurinol markedly inhibited the growth of amastigotes in a dose-dependent manner, with no lethal effect on trypomastigotes. 3'-Deoxyinosine and 3'-deoxyadenosine also suppressed T.cruzi growth inside the host cell, with IC_<50> values of 10 and 5 muM,respectively, in contrast to the value of 3 muM for allopurinol. Among pyrimidine analogs examined, 3'-azido-3'-deoxythymidine (AZT) significantly reduced the growth of the parasite at concentrations as low as 1 muM.The anti-HIV agents, 2', 3'-dideoxyinosine and 2', 3'-dideoxy adenosine, caused a decrease in amastigote growth, while 2', 3', -dideoxycytidine and 2', 3'-dideoxyuridine had no inhibitory effect. These results indicate that our culture system is useful as a primary screening method for candidate compounds against T.cruzi on the basis of two criteria, intracellular replication by the parasite and host-cell infection rate. Using this system, efficacies of calcium channel blockers, synthetic peptides, and natural planta components of Asian origen were also determined.
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