title: Design and Synthesis of Structure-Simplified Derivatives of Gonytolide for the Promotion of Innate Immune Responses.
abstract: Gonytolide A (1), a dimeric chromanone substituted with the γ-lactone, shows promoting activity of innate immune responses. However, biological studies on this compound have been limited by the low amounts of 1 available from natural resources and the difficulty of its synthesis. In this study, we designed and synthesized structure-simplified gonytolide derivatives. Bischromone 10 and biflavone 13 both promoted the mammalian TNF-α signaling pathway and Drosophila innate immunity. They did not contain a chiral center and were easy to synthesize. Hence, they can be used as lead compounds for a new type of immunostimulating drugs and as research reagents.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Tohoku University , Aoba-yama, Aoba-ku, Sendai 980-8578, Japan.
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: Tsuyoshi
authors.initials: T
authors.lastname: Hoshikawa
authors.affiliation: Graduate School of Pharmaceutical Sciences, Tohoku University , Aoba-yama, Aoba-ku, Sendai 980-8578, Japan.
authors.forename: Shoichiro
authors.initials: S
authors.lastname: Kurata
authors.affiliation: Graduate School of Pharmaceutical Sciences, Tohoku University , Aoba-yama, Aoba-ku, Sendai 980-8578, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Katou
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; D002867:Chromones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004330:Drosophila / Q000378:metabolism*; D015195:Drug Design; D007113:Immunity, Innate / Q000187:drug effects*; D007783:Lactones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D015398:Signal Transduction; D013237:Stereoisomerism; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism
chemical_list: D002867:Chromones; D007783:Lactones; D014409:Tumor Necrosis Factor-alpha; C000619006:gonytolide A