title: Synthesis of febrifugine derivatives and development of an effective and safe tetrahydroquinazoline-type antimalarial.
abstract: Febrifugine, a quinazoline alkaloid isolated from Dichroa febrifuga roots, shows powerful antimalarial activity against Plasmodium falciparum. Although the use of ferifugine as an antimalarial drug has been precluded because of its severe side effects, its potent antimalarial activity has stimulated medicinal chemists to pursue its derivatives instead, which may provide valuable leads for novel antimalarial drugs. In the present study, we synthesized new derivatives of febrifugine and evaluated their in vitro and in vivo antimalarial activities to develop antimalarials that are more effective and safer. As a result, we proposed tetrahydroquinazoline-type derivative as a safe and effective antimalarial candidate.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba-yama, Aoba-ku, Sendai 980-8578, Japan. Electronic address: hal@mail.pharm.tohoku.ac.jp.
authors.forename: Haruhisa
authors.initials: H
authors.lastname: Kikuchi
authors.affiliation: Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba-yama, Aoba-ku, Sendai 980-8578, Japan.
authors.forename: Seiko
authors.initials: S
authors.lastname: Horoiwa
authors.affiliation: Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba-yama, Aoba-ku, Sendai 980-8578, Japan.
authors.forename: Ryota
authors.initials: R
authors.lastname: Kasahara
authors.affiliation: Microbiological Research Institute, Otsuka Pharmaceutical Co., Ltd., 463-10 Kagasuno, Kawauchi-cho, Tokushima 771-0192, Japan.
authors.forename: Norimitsu
authors.initials: N
authors.lastname: Hariguchi
authors.affiliation: Microbiological Research Institute, Otsuka Pharmaceutical Co., Ltd., 463-10 Kagasuno, Kawauchi-cho, Tokushima 771-0192, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Matsumoto
authors.affiliation: Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba-yama, Aoba-ku, Sendai 980-8578, Japan.
authors.forename: Yoshiteru
authors.initials: Y
authors.lastname: Oshima
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D010880:Piperidines / Q000138:chemical synthesis* / Q000494:pharmacology; D010963:Plasmodium falciparum / Q000187:drug effects*; D011799:Quinazolines / Q000138:chemical synthesis* / Q000494:pharmacology; D016339:Spectrometry, Mass, Fast Atom Bombardment
chemical_list: D000962:Antimalarials; D010880:Piperidines; D011799:Quinazolines; C001207:febrifugine
keywords: Antimalarials; Plasmodium falciparum; Quinazoline alkaloids; Structure–activity relationship