69(P-55) 植物キナゾリンアルカロイドfebrifugineを基軸とする新規抗マラリア物質への展開(ポスター発表の部)

概要

論文の詳細を見る
Febrifugine (1) and isofebrifugine (2), isolated from the roots of Dichroa febrifuga Lour. (Chinese name: Chang Shan) are active principles against malaria. Clinical testing of febrifugine (1) was not successful, and the results of clinical evaluation are not yet available. To reinvestigate the antimalarial activity of these compounds, and to get functional informations to exhibit the activity, we set about studying febrifugine and its analogues. Adducts of febrifugine (1) and isofebrifugine (2) with acetone, Df-1 (3) and Df-2 (4), respectively, were obtained using silica gel and acetone. They showed high activity against P. falciparum malaria in vitro. Structure-activity relationships (SAR) studies on the antimalarial activity of febrifugine-analogues revealed that 4-quinazolinone moiety along with 1'-ketone, 5'-N atom and 9'-O-function are necessary to exhibit antimalarial activity. Moreover, Df-1 (3) was found to be equally effective to P. berghei in vivo as the clinically used drug chloroquine, whereas 4 showed only 1/24 activity of 3. Whole blood concentration of Df-2 (4) decreased more rapidly than that of Df-1 (3). This finding was accounted by the metabolism studies of these compounds by using S-9 mix prepared from mouse liver. Df-2 (4) was readily metabolized in mouse liver. Accordingly, the dose of Df-2 (4) must be higher than that of Df-1 (3) to attain blood levels sufficient for a favorable therapeutic effect.
天然有機化合物討論会の論文
2000-10-01

69(P-55) 植物キナゾリンアルカロイドfebrifugineを基軸とする新規抗マラリア物質への展開(ポスター発表の部)

スポンサーリンク

概要

著者

関連論文

スポンサーリンク