Author/Authors :
Michaël Prakesch، نويسنده , , Krikor Bijian، نويسنده , , Valérie Campagna-Slater، نويسنده , , Sophie Quevillon-Cheruel، نويسنده , , Reni Joseph، نويسنده , , Chang-Qing Wei، نويسنده , , Esther Sesmilo، نويسنده , , Ayub Reayi، نويسنده , , Rajamohan R. Poondra، نويسنده , , Michael L. Barnes، نويسنده , , Donald M. Leek، نويسنده , , Bin Xu، نويسنده , , Caroline Lougheed، نويسنده , , Matthieu Schapira، نويسنده , , Moulay Alaoui-Jamali، نويسنده , , Prabhat Arya، نويسنده ,
Abstract :
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.
Keywords :
Docking , Anti-cancer agents , Natural products , Natural product-like compounds , Small-molecule chemical probes , Diversity-oriented synthesis , focal adhesion kinase , Signaling networks , Cell migration