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Study of Reversal agents of chloroquine resistant Plasmodium falciparum

Research Project

Project/Area Number 13670254
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 寄生虫学(含医用動物学)
Research InstitutionKyorin University School of Medicine

Principal Investigator

KARUKI Kosuke  Kyorin University School of Medicine, Department of Infectious Diseases, Snior Lecturer, 医学部, 講師 (30286421)

Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2002: ¥1,700,000 (Direct Cost: ¥1,700,000)
KeywordsPlasmodium falciparum / Chloroquine / Reversal agents / Cepharanthin / N276 / クロロキン耐性 / 感受性克服 / アルカロイド / P糖蛋白 / 核移植
Research Abstract

The agents which may reverse chloroquine sensitivity of Plasmodium falciparum are investigated. Cepaharnthin a mixture of cepharanthine (CE), isotetrandrine (IT), berbamine (BE), homoalomoline (HO), cepharanoline (CO), cycleanine (CY) showed remarkable reversal effect against K1 strain. Fifty percent of inhibition concentration are CP 333.8^^+__-103.6nM, CE 1018.0^^+__-138.2, IT 169.8^^+__-27.4, BE 485.8^^+__-46.2, HO 1489.8^^+__-299.7, CO 1015.9^^+__-95.7, CY 3767.9^^+__-1993.8. Alkaloids except for CY are similar structure despite the results divided three groups in term of efficacy. There are relatively low IC_<50> group such as IT, BE, high group such as CE, HO, CO and CY which sowed no efficacy to malaria parasite. The reversal effect is highest with CP compare with single alkaloids as 15 times whilst CE 2, IT 9, BE 4, HO 2, CO 3, CY 1.5 times. CP the mixture of these 6 alkaloids showed most effective combination and expected for clinical use in future. The novel P-glycoprotein inhibitor N276 series developed by Nikken Kagaku Co, had been investigated also as same method using cepharanthin. N-276-15 showed same value of reversal as same as standard chemosensitizer Verapamkl. N-276-5, 17, 26 and 27 showed no reversal with K1 strain. Those two experiments suggested that P-glycoprotein may not be strongly related with chloroquine resistant mechanism of Plasmodium falciparum.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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