2000 Fiscal Year Final Research Report Summary
Chemical Investigation of Antimalarial Compounds from Marine Organisms
| Project/Area Number |
11672107
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Chemical pharmacy
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| Research Institution | University of the Ryukyus |
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Principal Investigator |
HIGA Tatsuo University of the Ryukyus, college of Science Professor, 理学部, 教授 (10101461)
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| Co-Investigator(Kenkyū-buntansha) |
TANAKA Junichi University of the Ryukyus, College of Science Associate Professor, 理学部, 助教授 (20163529)
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| Project Period (FY) |
1999 – 2000
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| Keywords | Antimalarial drugs / Marine Natural Products / Manzamines |
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| Research Abstract |
Malaria is one of the most important infectious diseases. It is estimated to inflict more than 300 million people and to kill some two million people a year in the world. Chemotherapy is still the most effective method of treatment of the disease. However, because of the emergence of resistant parasites against the most frequently used drugs such as chloroquine, it is necessary to develop new effective and safe drugs. In this project we have screened in collaboration with Dr. A.U.Kara more than 100 compounds isolated from marine organisms. The screening was an in vivo test using mice infected with the rodent malaria parasite Plasmodiun berghei. Drugs of the doses ranging from 50 to 1000 μM/kg were injected to the mice on day 2 of postinfection and recorded the days and numbers of surviving mice. As a result manzamine A, a complex alkaloid from a sponge, was shown to be most effective antimalarial. Efficacy of manzamine A was compared with artemisinin and chloroquine. Manzamine A at a single dose of 100 μM/kg gave the best result with 40% recovery, survival of two out of five mice for 60 days postinfection. Artemisinin gave 20% recovery at a dose of 1000 μM/kg, while the treatment with chloroquine gave no recovery, all mice died by day 10. In order to examine structure activity relationship of the manzamine alkaloids, we have prepared Several derivatives of manzamine A.They were similarly tested together with 8-hydroxymanzamine A and manzamine F which have also been isolated from sponges. Only 8-hydroxymanzamine A showed some efficacy, but all others were not active. The result suggested that the complex framework of manzamine A would be important for the activity. Further work is needed to clarify the structure activity relationship and mechanism of the action of manzamine A.
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