2010 Fiscal Year Final Research Report
Natural Product Hybrids : Design, Synthesis and Evaluation of Novel Antimicrobial Agents
| Project/Area Number |
21890262
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Single-year Grants |
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| Research Field |
Drug development chemistry
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| Research Institution | Tokyo University of Pharmacy and Life Science |
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Principal Investigator |
YAKUSHIJI Fumika Tokyo University of Pharmacy and Life Science, 薬学部, 助教 (40548476)
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| Project Period (FY) |
2009 – 2010
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| Keywords | ハイブリッド / 抗菌活性 / RNAポリメラーゼ / Holothin / Myxopyronin / Thiomarinol |
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| Research Abstract |
1)Previously, the total syntheses of hybrid type natural products ‘thiomarinols' were accomplished by author. Thiomarinols were found to exhibit potent antimicrobial activity, which came from hybrid structure : pseudomonic acid part and holothin part. Based on the synthetic pathway, hybrid type derivatives as antimicrobial agents were designed and synthesized. The structure-activity relationship studies and optimization are now in progress.
2)Myxopyronins were isolated from Myxococcus fulvus Mx f50 and found to exhibit antimicrobial activity, which inhibition mechanism was reported as a novel pathway. However, myxopyronin revealed high lipophilicity and limited membrane permeability which are inadequate aspects for a drug. This time, design and synthesis of novel hybrid-type derivatives of myxopyronins with the strategy of linking holothin part, which included in thiomarionols, were attempted to improve lipophilicity and cell permeability for broad antibacterial spectrum. Synthesized derivatives were evaluated as antimicrobial agents, and some derivatives showed more potent activity than myxopyronins against gram-positive bacterias on minimal inhibitory concentration (MIC) results. According to this hybrid strategy, novel antimicrobial derivatives were obtained and structural optimization is now in progress.
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[Presentation] Synthesis of (+)-Negamycin and Derivatives2009
Author(s)
Yakushiji F., Nishiguchi S., Sydnes O.M., Taguchi A., Regnier T., Kajimoto T., Node M., Kiso Y., Yamazaki Y., Hayashi Y.
Organizer
3^<rd> Asia-Pasific International Peptide Synposium
Place of Presentation
Jeju, KOREA
Year and Date
20091108-20091111
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