Building skeletally diverse architectures on the Indoline Scaffold: the discovery of a chemical probe of focal adhesion kinase signaling networks.
Inspired by bioactive indoline alkaloid natural products, here, we report a divergent synthesis approach that led to skeletally diverse indoline alkaloid-inspired compounds. The natural product-inspired compounds obtained were then subjected to a series of in vitro and cellular assays to examine their properties as modulators of focal adhesion kinase (FAK) activity. This study resulted in the identification of a promising lead inhibitor of FAK (42), which also showed activity in a wound healing and cell invasion assay. The in silico study of the lead compound (42) was also undertaken.
Prakesch
Michael
M
Ontario Institute for Cancer Research, MaRS Centre, South Tower, 101 College Street, Toronto, Ont., Canada M5G0A3.
Bijian
Krikor
K
Campagna-Slater
Valérie
V
Quevillon
Sophie
S
Joseph
Reni
R
Wei
Chang-Qing
CQ
Sesmilo
Esther
E
Reayi
Ayub
A
Poondra
Rajamohan R
RR
Barnes
Michael L
ML
Leek
Donald M
DM
Xu
Bin
B
Lougheed
Caroline
C
Schapira
Matthieu
M
Alaoui-Jamali
Moulay
M
Arya
Prabhat
P
D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003198:Computer Simulation; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D006801:Humans; D026121:Indole Alkaloids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects*; D014407:Tumor Cells, Cultured; D014945:Wound Healing / Q000187:drug effects
D004791:Enzyme Inhibitors; D026121:Indole Alkaloids; D007211:Indoles; C057812:indoline; D051416:Focal Adhesion Protein-Tyrosine Kinases