title: Development of novel DIF-1 derivatives that selectively suppress innate immune responses.
abstract: The multiple pharmacological activities of differentiation-inducing factor-1 (DIF-1) of the cellular slime mold Dictyostelium discoideum led us to examine the use of DIF-1 as a 'drug template' to develop promising seed compounds for drug discovery. DIF-1 and its derivatives were synthesized and evaluated for their regulatory activities in innate immune responses. We found two new derivatives (4d and 5e) with highly selective inhibitory activities against production of the antimicrobial peptide attacin in Drosophila S2 cells and against production of interleukin-2 in Jurkat cells.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba-yama, Aoba-ku, Sendai 980-8578, Japan.
authors.forename: Van Hai
authors.initials: VH
authors.lastname: Nguyen
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: Department of Molecular and Cellular Biology, Institute for Molecular and Cellular Regulation (IMCR), Gunma University, 3-39-15 Showa-machi, Maebashi, Gunma 371-8512, Japan; Graduate School of Health and Sports Science, Juntendo University, 1-1 Hiraga-gakuendai, Inzai, Chiba 270-1695, Japan.
authors.forename: Yuzuru
authors.initials: Y
authors.lastname: Kubohara
authors.affiliation: Department of Medical Technology, Faculty of Health Science, Gunma Paz College, Takasaki 370-0006, Japan.
authors.forename: Katsunori
authors.initials: K
authors.lastname: Takahashi
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; D030801:Animals, Genetically Modified; D001554:Benzene / Q000737:chemistry; D060326:Chemistry Techniques, Synthetic; D004023:Dictyostelium; D004330:Drosophila / Q000166:cytology / Q000276:immunology; D055808:Drug Discovery; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006588:Hexanones / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects*; D007166:Immunosuppressive Agents / Q000737:chemistry* / Q000494:pharmacology*; D019476:Insect Proteins / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D019169:Jurkat Cells / Q000187:drug effects / Q000378:metabolism
chemical_list: D006588:Hexanones; D007166:Immunosuppressive Agents; D019476:Insect Proteins; D007376:Interleukin-2; C039711:attacin antibacterial protein, insect; C053433:1-((3,5-dichloro)-2,6-dihydroxy-4-methoxyphenyl)-1-hexanone; D001554:Benzene
keywords: Cellular slime mold; Drosophila; Immunosuppressor; Innate immunity; Structure–activity relationship