Search for new natural products ligands having effects on disease and development pathways

2015 Fiscal Year Final Research Report

• Project Area: Chemical Biology using bioactive natural products as specific ligands: identification of molecular targets and regulation of bioactivity
• Project/Area Number: 23102008
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Science and Engineering
• Research Institution: Chiba University
• Principal Investigator: Ishibashi Masami 千葉大学, 薬学研究科(研究院), 教授 (90212927)
• Co-Investigator(Kenkyū-buntansha): ARAI A. Midori 千葉大学, 大学院薬学研究院, 准教授 (40373261) ; TOUME Kazufumi 千葉大学, 大学院薬学研究院, 助教 (80563981) ; ISHIKAWA Naoki 千葉大学, 大学院薬学研究院, 助教 (20748826)
• Project Period (FY): 2011-04-01 – 2016-03-31
• Keywords: シグナル伝達 / 生理活性 / 薬学 / 生体分子 / 有機化学

Outline of Final Research Achievements

Screening programs targeting biological pathways such as TRAIL, Wnt, and Hedgehog signaling and bHLH transcriptional factors resulted in isolation of a variety of bioactive compounds from our natural products collection and natural products based synthetic compounds such as calotropin, a caldenolide with Wnt signal inhibitory activity through enhancement of mRNA expression of casein kinase 1α, artonin E, a prenylated flavone with TRAIL resistance overcoming activity, and vitetrifolin D, a diterpene with hedgehog signal inhibitory activity. Search for Hes1 dimer inhibitors by target protein oriented natural products isolation (TPO-NAPI) using Hes1-beads HPLC system was examined for rapid discovery of natural products with differentiation activating effects of neural stem cells to yield agalloside, a flavonoid glycoside from extract of Aquilaria agallocha (Thymelaeaceae), and inohanamine, a new piperidine alkaloid with a triene side chain, isolated from a Streptomyces strain IFM11584.

Free Research Field

天然物化学