PUBLICATION

Identification of noreremophilane-based inhibitors of angiogenesis using zebrafish assays

Authors
Muthukumarasamy, K.M., Handore, K.L., Kakade, D.N., Shinde, M.V., Ranjan, S., Kumar, N., Sehrawat, S., Sachidanandan, C., Reddy, D.S.
ID
ZDB-PUB-151021-11
Date
2016
Source
Organic & biomolecular chemistry   14(5): 1569-78 (Journal)
Registered Authors
Keywords
none
MeSH Terms
  • Angiogenesis Inhibitors/chemical synthesis
  • Angiogenesis Inhibitors/chemistry
  • Angiogenesis Inhibitors/pharmacology*
  • Animals
  • Embryo, Nonmammalian/blood supply*
  • Embryo, Nonmammalian/drug effects*
  • Embryo, Nonmammalian/pathology
  • Humans
  • Molecular Conformation
  • Neovascularization, Pathologic/drug therapy*
  • Sesquiterpenes/chemical synthesis
  • Sesquiterpenes/chemistry
  • Sesquiterpenes/pharmacology*
  • Xenograft Model Antitumor Assays
  • Zebrafish/embryology*
PubMed
26483278 Full text @ Org. Biomol. Chem.
Abstract
Noreremophilanes are a rare class of cis-hydrindanes produced by genus Ligularia herbaceous plants which are known to exhibit interesting biological activities. We synthesized cis-hydrindanes based on a naturally occurring noreremophilane scaffold using a Diels-Alder/aldol sequence and screened them for multiple biological activities using high-content zebrafish embryonic development assays. We discovered a noreremophilane that has strong anti-angiogenic effects on the developing zebrafish embryos as well as on tumor-induced angiogenesis in a zebrafish xenograft model. We synthesized several derivatives of this class of noreremophilanes and performed structure-activity relationship studies in zebrafish to identify more potent and less toxic analogs of the original structure.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping