Identification of noreremophilane-based inhibitors of angiogenesis using zebrafish assays.
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.
CSIR-Institute of Genomics & Integrative Biology (CSIR-IGIB), South Campus, New Delhi, 110025, India. chetana@igib.in.
Kalai Mangai
KM
Muthukumarasamy
CSIR-National Chemical Laboratory (CSIR-NCL), Division of Organic Chemistry, Dr Homi Bhabha Road, Pune, 411008, India. ds.reddy@ncl.res.in and Academy of Scientific and Innovative Research (AcSIR), 110025, New Delhi, India.
Kishor L
KL
Handore
CSIR-National Chemical Laboratory (CSIR-NCL), Division of Organic Chemistry, Dr Homi Bhabha Road, Pune, 411008, India. ds.reddy@ncl.res.in.
Dipti N
DN
Kakade
CSIR-National Chemical Laboratory (CSIR-NCL), Division of Organic Chemistry, Dr Homi Bhabha Road, Pune, 411008, India. ds.reddy@ncl.res.in.
Madhuri V
MV
Shinde
CSIR-Institute of Genomics & Integrative Biology (CSIR-IGIB), South Campus, New Delhi, 110025, India. chetana@igib.in.
Shashi
S
Ranjan
Vascular Biology Lab, Department of Life Sciences, School of Natural Sciences, Shiv Nadar University, India.
Naveen
N
Kumar
Vascular Biology Lab, Department of Life Sciences, School of Natural Sciences, Shiv Nadar University, India.
Seema
S
Sehrawat
CSIR-Institute of Genomics & Integrative Biology (CSIR-IGIB), South Campus, New Delhi, 110025, India. chetana@igib.in.
Chetana
C
Sachidanandan
CSIR-National Chemical Laboratory (CSIR-NCL), Division of Organic Chemistry, Dr Homi Bhabha Road, Pune, 411008, India. ds.reddy@ncl.res.in and Academy of Scientific and Innovative Research (AcSIR), 110025, New Delhi, India.
D Srinivasa
DS
Reddy
D020533:Angiogenesis Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D004625:Embryo, Nonmammalian / Q000098:blood supply* / Q000187:drug effects* / Q000473:pathology; D006801:Humans; D008968:Molecular Conformation; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D012717:Sesquiterpenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays; D015027:Zebrafish / Q000196:embryology*
D020533:Angiogenesis Inhibitors; D012717:Sesquiterpenes; C584911:noreremophilane