Bovine Serum Amine Oxidase and Polyamine Analogues: Chemical Synthesis and Biological Evaluation Integrated with Molecular Docking and 3-D QSAR Studies

Natural polyamines (PAs) are key players in cellular homeostasis by regulating cell growth and proliferation. Several observations highlight that PAs are also implicated in pathways regulating cell death. Indeed, the PA accumulation cytotoxic effect, maximized with the use of bovine serum amine oxidase (BSAO) enzyme, represents a valuable strategy against tumor progression. In the present study, along with the design, synthesis, and biological evaluation of a series of new spermine (Spm) analogues (1-23), a mixed structure-based (SB) and ligand-based (LB) protocol was applied. Binding modes of BSAO-PA modeled complexes led to clarify electrostatic and steric features likely affecting the BSAO-PA biochemical kinetics. LB and SB three-dimensional quantitative structure-activity relationship (Py-CoMFA and Py-ComBinE) models were developed by means of the 3d-qsar.com portal, and their analysis represents a strong basis for future design and synthesis of PA BSAO substrates for potential application in oxidative stress-induced chemo-therapy.

Automated summary

Natural polyamines play important roles in regulating cell growth and proliferation, as well as in modulating cell death pathways. This study investigated the cytotoxic effects of polyamine accumulation, particularly with the use of bovine serum amine oxidase (BSAO) enzyme, which showed promise in inhibiting tumor progression. New spermine analogues were synthesized and evaluated, and a mixed structure-based and ligand-based approach was applied to analyze the binding modes of BSAO-polyamine complexes. The developed three-dimensional quantitative structure-activity relationship models provide a foundation for future design and synthesis of BSAO substrates with potential applications in oxidative stress-induced chemotherapy.