Premium
Antimalarial activities of gedunin and 7‐methoxygedunin and synergistic activity with dillapiol
Author(s) -
OMAR S,
GODARD K,
INGHAM A,
HUSSAIN H,
WONGPANICH V,
PEZZUTO J,
DURST T,
EKLU C,
GBEASSOR M,
SANCHEZVINDAS P,
POVEDA L,
PHILOGENE B J R,
ARNASON J T
Publication year - 2003
Publication title -
annals of applied biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.677
H-Index - 80
eISSN - 1744-7348
pISSN - 0003-4746
DOI - 10.1111/j.1744-7348.2003.tb00279.x
Subject(s) - pharmacology , biology , in vivo , plasmodium berghei , pharmacokinetics , immunology , microbiology and biotechnology , malaria
Summary Gedunin from Cedrela odorata (Meliaceae), a potent in vitro antimalarial agent, was investigated for its in vivo efficacy in CD‐1 mice infected with Plasmodium berghei . When orally administered at 50 mg kg‐1 day‐1 for 4 days, gedunin was able to suppress the parasitaemia level by 44%. However, no clear dose‐response effects were observed in the 0–100 mg kg‐1 day‐1 dose range. Preliminary pharmacokinetics in Sprague‐Dawley rats showed poor absorption. However, a binary treatment of 50 mg kg‐1 day‐1 gedunin with 25 mg kg‐1 day‐1 dillapiol, a cytochrome P450 inhibitor, increased parasitaemia clearance in mice to 75%. A clear dose‐response was observed in the 0–50 mg kg‐1 day‐1 gedunin dose range when administration was combined with 25 mg kg‐1 day‐1 dillapiol. In addition, 7‐methoxygedunin, a semi‐synthetic derivative which is more stable to degradation than gedunin, suppressed the level in mice by 67% at 50 mg kg‐1 day‐1. When administered at this dose in combination with 25 mg kg‐1 day‐1 dillapiol, clearance increased to 80%. These results demonstrate the potentialefficacy of antimalarial drugs and phytomedicines based on gedunin and the value of the combination therapy.