title: Aza-derivatives of resveratrol are potent macrophage migration inhibitory factor inhibitors.
abstract: Resveratrol (3, 4', 5-trihydroxy-trans-stilbene), a natural phytoalexin found in grapes and wine, has anti-proliferative activity on human-derived cancer cells. In our study, we used a conventional condensation reaction between aldehydes and amines to provide a number of aza-resveratrol (3, 4', 5-trihydroxy-trans- aza-stilbene) derivatives in an attempt to screen for compounds with resveratrol's action but with increased potency. Aza-resveratrol and its hydroxylated derivative (3, 4, 4', 5-tetrahydroxy-trans- aza-stilbene) showed a more enhanced anti-proliferative effect than resveratrol in an MCF-7 breast carcinoma cell line. To identify the cellular targets of the aza derivatives of resveratrol, we conjugated the latter aza-stilbene compound with epoxy-activated agarose and performed affinity purification. Macrophage migration inhibitory factor (MIF), a proinflammatory cytokine, was identified as a major target protein in MCF-7 cell lysates using a matrix-assisted laser desorption/ionization time-of-flight mass spectrometer (MALDI-TOF MS). The aza-resveratrol and its hydroxylated derivative, but not resveratrol, were also found to be potent inhibitors of MIF tautomerase activity, which may be associated with their inhibitory effects on MIF bioactivity for cell growth.
authors.affiliation: Department of Genome Biology, Kinki University School of Medicine, Osaka-Sayama, 589-8511, Osaka, Japan.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Fujita
authors.forename: Rafiqul
authors.initials: R
authors.lastname: Islam
authors.forename: Kazuko
authors.initials: K
authors.lastname: Sakai
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Kaneda
authors.forename: Kanae
authors.initials: K
authors.lastname: Kudo
authors.forename: Daisuke
authors.initials: D
authors.lastname: Tamura
authors.forename: Keiichi
authors.initials: K
authors.lastname: Aomatsu
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Nagai
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Kimura
authors.forename: Kazuko
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Marco A
authors.initials: MA
authors.lastname: de Velasco
authors.forename: Tokuzo
authors.initials: T
authors.lastname: Arao
authors.forename: Tadashi
authors.initials: T
authors.lastname: Okawara
authors.forename: Kazuto
authors.initials: K
authors.lastname: Nishio
mesh_terms: D000595:Amino Acid Sequence; D001372:Aza Compounds / Q000138:chemical synthesis / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D008263:Macrophage Migration-Inhibitory Factors / Q000037:antagonists & inhibitors*; D008969:Molecular Sequence Data; D000077185:Resveratrol; D013267:Stilbenes / Q000737:chemistry
chemical_list: D001372:Aza Compounds; D008263:Macrophage Migration-Inhibitory Factors; D013267:Stilbenes; D000077185:Resveratrol