2005 Fiscal Year Final Research Report Summary
Research and Development of the New Antiviral Drugs by Remodeling of the New Diterpenoid Isolated from Sea Algae
| Project/Area Number |
15590097
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Drug development chemistry
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| Research Institution | University of Toyama (2005)
Toyama Medical and Pharmaceutical University (2003-2004) |
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Principal Investigator |
IWASHIMA Makoto University of Toyama, Faculty of Pharmaceutical Sciences, Associate Prof., 薬学部, 助教授 (20266901)
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| Co-Investigator(Kenkyū-buntansha) |
HAYASHI Kyoko University of Toyama, School of Medicine, Research Assistant, 医学部, 助手 (60110623)
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| Project Period (FY) |
2003 – 2005
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| Keywords | Plastoquinone / Antiviral Activity / Chromene Derivatives / Brown Alga / Sargassum micracanthum / Marine Natural Products / Antioxidative Activity / Structure-Activity Relationship |
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| Research Abstract |
In the screening study for investigation of a new antiviral compound, the authors found the chromene derivative 1 from the brown alga Sargassum micracanthum along with some known plastoquinones. More careful isolation revealed compound 1 possessing a strong antiviral activity against HSV,HIV and HCMV to be an artifact, converted from the known plastoquinones in the isolation process ; however, these plastoquinones did not show antiviral effect even for HSV-1. The authors started to find much more active compound similar to 1 by SAR method, including the remodeling of chromene 1,polymer-supported derivatives and the analogs of 1 hybridized with some delivery peptides. Totally twelve analogs were synthesized from the plastoquinones and commercially available simple compounds. According to the bioassay of them, four chromenes converted from the known plastoquinones showed strong antiviral activity against HSV-1,HSV-2,HCMV, Influenza and HIV as much as that of 1. Moderate antiviral activity against HSV was observed from the remaining eight compounds in vitro. According to the data, the chromene structure is the crucial for expressing the antiviral activity. These chromenes might be inhibited reverse-transcriptase (RT) and some chemokine receptor such as CCR5 in the primitive analysis of HIV infection. The activity of polymer-supported chromenes were still under investigation. In addition, the author continued to find the new bioactive compounds from algae. Four new antioxidative plastoquinones related the above-mentioned ones were isolated from S.micracanthum. Unfortunately, these new compounds did not exhibit antiviral effect. From the other brown algae related S.micracanthum, a lot of known compounds were obtained such as antioxidative carotenoids (a kind of fucoxanthine), cytotoxic terpenoids and fatty acid derivatives (glycerides and oxylipins). These results were already published, and see the references and patent.
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Research Products
(9 results)
