title: Anti-trypanosomal activity of diarylheptanoids isolated from the bark of Alnus japonica.
abstract: The crude extract of Alnus japonica bark exhibited a strong effect on the growth of Trypanosoma brucei. Subsequent chromatographic separation resulted in the isolation of two novel diarylheptanoids, known as alnuside C (2) and alnuside D (3), and three known compounds, 1-(3,4-dihydroxyphenyl)-7-(4-hydroxyphenyl)-heptan-3(R)-O-β-D-glucopyranoside (1), oregonin (4) and hirsutanone (5). The structures of the isolates were elucidated based on the use of extensive spectroscopic and chemical methods. Among the isolated diarylheptanoids, oregonin (4) (a major component of plant bark) and hirsutanone (5) exhibited potent in vitro inhibitory activity against T. brucei growth in the bloodstream with IC50 values of 1.14 and 1.78 μM, respectively. We confirmed that oregonin (4) and hirsutanone (5) were not toxic to human normal skin fibroblast cells (NB1RGB) and colon cancer cells (HCT-15) at a concentration of 50 μM; however, lower levels of toxicity were observed for leukemia cells. To determine the structure activity relationships of the isolated components, we performed Conformation Search and found that the 3-oxo function of the heptane chain in the diarylheptanoid molecule is required for their trypanocidal activity.
authors.affiliation: Faculty of Pharmaceutical Sciences, Nagasaki International University, Sasebo, Nagasaki 859-3298, Japan.
authors.forename: Nguyen Huu
authors.initials: NH
authors.lastname: Tung
authors.forename: Mitsuko
authors.initials: M
authors.lastname: Suzuki
authors.forename: Takuhiro
authors.initials: T
authors.lastname: Uto
authors.forename: Osamu
authors.initials: O
authors.lastname: Morinaga
authors.forename: Kofi D
authors.initials: KD
authors.lastname: Kwofie
authors.forename: Naa
authors.initials: N
authors.lastname: Ammah
authors.forename: Kwadwo A
authors.initials: KA
authors.lastname: Koram
authors.forename: Frederic
authors.initials: F
authors.lastname: Aboagye
authors.forename: Dominic
authors.initials: D
authors.lastname: Edoh
authors.forename: Taizo
authors.initials: T
authors.lastname: Yamashita
authors.forename: Yasuchika
authors.initials: Y
authors.lastname: Yamaguchi
authors.forename: Takao
authors.initials: T
authors.lastname: Setsu
authors.forename: Shoji
authors.initials: S
authors.lastname: Yamaoka
authors.forename: Nobuo
authors.initials: N
authors.lastname: Ohta
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Shoyama
mesh_terms: D029661:Alnus; D000818:Animals; D002478:Cells, Cultured; D003110:Colonic Neoplasms / Q000473:pathology; D036381:Diarylheptanoids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007938:Leukemia / Q000473:pathology; D024301:Plant Bark; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D012867:Skin / Q000166:cytology; D013329:Structure-Activity Relationship; D014344:Trypanocidal Agents; D014346:Trypanosoma brucei brucei / Q000187:drug effects* / Q000254:growth & development*; D014407:Tumor Cells, Cultured
chemical_list: D036381:Diarylheptanoids; D010936:Plant Extracts; D014344:Trypanocidal Agents
keywords: Alnus japonica; Anti-Trypanosomal Activity; Diarylheptanoid; Oregonin; Trypanosoma brucei