Structure-based lead optimization and biological evaluation of BAX direct activators as novel potential anticancer agents

  • J Med Chem. 2015 Mar 12;58(5):2135-48. doi: 10.1021/jm501123r.
Mariano Stornaiuolo  1 ,  Giuseppe La Regina ,  Sara Passacantilli ,  Gianluca Grassia ,  Antonio Coluccia ,  Valeria La Pietra ,  Mariateresa Giustiniano ,  Hilde Cassese ,  Salvatore Di Maro ,  Diego Brancaccio ,  Sabrina Taliani ,  Armando Ialenti ,  Romano Silvestri ,  Claudia Martini ,  Ettore Novellino ,  Luciana Marinelli
Affiliations
  • 1. Dipartimento di Farmacia, Università di Napoli "Federico II" , via D. Montesano 49, 80131 Naples, Italy.
PMID: 25668341 DOI: 10.1021/jm501123r
Abstract

The first direct activator of Bax, a pro-apoptotic member of the Bcl-2 Family, has been recently identified. Herein, a structure-based lead optimization turned out into a small series of analogues, where 8 is the most potent compound published so far. 8 was used as pharmacological tool to ascertain, for the first time, the Anticancer potential of Bax direct activators and the obtained results would suggest that Bax direct activators are potential future Anticancer drugs rather than venoms.