A combined structure and ligand-based application on BSAO as an encouraging approach in anti-cancer therapy.

Bovine serum amine oxidase (BSAO) is a copper-containing enzyme that catalyzes the oxidation of primary amines, such natural polyamines spermine and spermidine, into their corresponding aldehydes, to release the cytotoxic hydrogen peroxide and ammonia. Since these products were recognized to induce stress-activated signal transduction pathways, determining necrosis or apoptosis in tumor-cultured cell lines,1 new strategies are emerging2 for anti-cancer treatments with BSAO and the development of new polyamine analogs is mandatory. To improve enzyme-substrate affinity, structure based (SB) and ligand based (LB) studies were performed on 25 among natural polyamines and newly synthesized and biologically assayed polyamine analogs. The connubium3 between the AutoDock suite,4 3-D QSAutogrid/R5 and COMBINEr6, 7 methodologies, allowed to define the most influent ligand-residues interactions and derive a predictive 3-D QSAR pharmacophoric model as a promising paradigm to predict and design novel BSAO substrates, endowed with both high potency and selectivity. As future perspective, these molecules will be biologically tested as BSAO substrates to evaluate their cytotoxic effects and eligibility to be used in this new anti-cancer therapy. Details and methodologies will be reported.