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ACS Med Chem Lett. 2017 Sep 12;8(10):1066-1071. doi: 10.1021/acsmedchemlett.7b00281. eCollection 2017.

New Scaffold for Angiogenesis Inhibitors Discovered by Targeted Chemical Transformations of Wondonin Natural Products.

Author information

  • 1College of Pharmacy, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Korea.

Abstract

The structure of wondonin marine natural products was renovated to attain new drug-like scaffolds. Wondonins have novel antiangiogenic properties without overt cytotoxicity. However, the chemical instability and synthetic complexity of wondonins have hindered their development as a new type of antiangiogenesis agent. Using a structure-based bioisosterism, the benzodioxole moiety was changed to benzothiazole, and the imidazole moiety was replaced by 1,2,3-triazole. Our efforts resulted in a new scaffold with enhanced antiangiogenic activity and minimized cytotoxicity. One compound with this scaffold effectively inhibited hyaloid vessel formation in diabetic retinopathy mimic zebrafish model. The biological findings together suggested the potential of the scaffold as a lead structure for development of antiangiogenic drugs with novel functions and as a probe to elucidate new biological mechanisms associated with angiogenesis.

KEYWORDS:

Angiogenesis; VEGF/VEGFR2 pathway; diabetic retinopathy; drug design; wondonins

PMID:
29057052
PMCID:
PMC5641963
[Available on 2018-10-12]
DOI:
10.1021/acsmedchemlett.7b00281
[PubMed]
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