Exploration of a new type of antimalarial compounds based on febrifugine

Haruhisa Kikuchi, Keisuke Yamamoto, Seiko Horoiwa, Shingo Hirai, Ryota Kasahara, Norimitsu Hariguchi, Makoto Matsumoto, Yoshiteru Oshima

Research output: Contribution to journalArticlepeer-review

125 Citations (Scopus)

Abstract

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 because of 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 (i) the quinazoline ring, (ii) the linker, or (iii) the piperidine ring. Then, we evaluated their antimalarial activities. Thienopyrimidine analogue 15 exhibited a potent antimalarial activity and a high therapeutic selectivity both in vitro and in vivo, suggesting that 15 is a good antimalarial candidate.

Original languageEnglish
Pages (from-to)4698-4706
Number of pages9
JournalJournal of Medicinal Chemistry
Volume49
Issue number15
DOIs
Publication statusPublished - 2006 Jul 27
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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