title: Approaches to neural stem cells and cancer cells based on natural products.
abstract: We have developed "protein- and cell-based screen methods" for the isolation of new natural products. By using VDR (vitamin D receptor) immobilized magnetic beads, two new natural products were isolated rapidly. To find inhibitors of Hes1 protein, which is one of the important transcriptional factors in neural stem cells, a Hes1 dimer plate assay was developed, and then first Hes1 dimer inhibitors were found from our natural products library. As a "cell-based screen method," a reporter gene assay for screening Hh (hedgehog) signaling inhibitors was constructed. New Hh signaling inhibitors were isolated from our natural extracts library. We evaluated their Hh inhibitory activity in Hh related protein synthesis and cytotoxicity against cancers, in which Hh signaling is aberrantly activated. In addition to the naturally made compounds library (extracts library), "small molecules based on natural products" were synthesized. The total synthesis of Melleumin A, B, which were isolated by our group, was achieved. From their synthetic derivatives, inhibitors of the Wnt signal, which has been reported to cause colon cancers, were discovered. Moreover, flavanone and chromone were selected as natural product scaffolds. Many flavonoids and chromones with diverse heterocyclic units were constructed using our efficient synthetic method.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Chiba University, 1–33 Yayoi-cho, Inage-ku, Chiba, Japan. marai@faculty.chiba-u.jp
authors.forename: Midori A
authors.initials: MA
authors.lastname: Arai
mesh_terms: D051792:Basic Helix-Loop-Helix Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D001688:Biological Products / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D047630:Depsipeptides / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity; D053823:Hedgehog Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D018398:Homeodomain Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D058953:Neural Stem Cells / Q000378:metabolism*; D015398:Signal Transduction; D000072056:Transcription Factor HES-1; D051153:Wnt Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D001688:Biological Products; D047630:Depsipeptides; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins; D000072056:Transcription Factor HES-1; D051153:Wnt Proteins; C539389:melleumin A; C539390:melleumin B; C078493:HES1 protein, human