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 chemotherapy.