P-43 多様なfebrifugine誘導体の合成と抗マラリア活性(ポスター発表の部)

概要

論文の詳細を見る
Malaria is a one of the serious parasitic infections in many tropical and subtropical regions. Plasmodium falciparum is becoming resistant to several antimalarials such as quinine, chloroquine, artemisinin and atovaquone. Therefore, the discovery of new and effective antimalarial drug is required. The clinical utilities of quinine and artemisinin have stimulated much interest in plants as potential sources of new antimalarial agents. Febrifugine (1), a quinazoline alkaloid, isolated from Dichroa febrifuga roots, shows powerful antimalarial activity against Plasmodium falciparum. The use of 1 as an antimalarial drug has been precluded due to side effects such as diarrhea, vomiting, and liver toxicity. However, the potent antimalarial activity of 1 has stimulated medicinal chemists to pursue compounds derived from 1, which may be valuable leads for novel drugs. In this study, we synthesized a new series of febrifugine derivatives formed by structural modifications at either the quinazoline ring, the linker, or the piperidine ring. Then we evaluated their antimalarial activities. Thienopyrimidine analog 13 exhibited a potent antimalarial activity and a high therapeutic selectivity both in vitro and in vivo, suggesting that 13 is a good antimalarial candidate.
天然有機化合物討論会の論文
2006-09-15