16 research outputs found
Spermine oxidase (SMO) activity in breast tumor tissues and biochemical analysis of the anticancer spermine analogues BENSpm and CPENSpm
Background: Polyamine metabolism has a critical role in cell death and proliferation representing a potential
target for intervention in breast cancer (BC). This study investigates the expression of spermine oxidase (SMO) and
its prognostic significance in BC. Biochemical analysis of Spm analogues BENSpm and CPENSpm, utilized in
anticancer therapy, was also carried out to test their property in silico and in vitro on the recombinant SMO
enzyme.
Methods: BC tissue samples were analyzed for SMO transcript level and SMO activity. Student’s t test was applied
to evaluate the significance of the differences in value observed in T and NT samples. The structure modeling
analysis of BENSpm and CPENSpm complexes formed with the SMO enzyme and their inhibitory activity, assayed
by in vitro experiments, were examined.
Results: Both the expression level of SMO mRNA and SMO enzyme activity were significantly lower in BC samples
compared to NT samples. The modeling of BENSpm and CPENSpm complexes formed with SMO and their
inhibition properties showed that both were good inhibitors.
Conclusions: This study shows that underexpression of SMO is a negative marker in BC. The SMO induction is a
remarkable chemotherapeutical target. The BENSpm and CPENSpm are efficient SMO inhibitors. The inhibition
properties shown by these analogues could explain their poor positive outcomes in Phases I and II of clinical trials
Rational drug design applied to myeloperoxidase inhibition
Rational drug design is a general approach using protein-structure technique in which the discovery of a ligand can be driven either by chance, screening, or rational theory. Myeloperoxidase (MPO) was rapidly identified as a therapeutical target because of its involvement in chronic inflammatory syndromes. In this context, the research of MPO inhibitors was intensified and development of new chemical entities was rationally driven by the research of ligands that enter into the MPO catalytic pocket. Actually, as soon as crystallography data of MPO have become available and its structure was virtually designed, the rational drug design has been applied to this peroxidase. Pharmaceutical industries and academic laboratories apply rational drug design on MPO by either optimizing known inhibitors or searching new molecules by high-throughput virtual screening. By these ways, they were able to find efficient MPO inhibitors and understand their interactions with the enzyme. During this quest of MPO inhibition, it appears that Glu268 is a crucial residue in order to optimize ligandtarget interaction. This amino acid should be carefully considered by medicinal chemist when they design inhibitors interfering with MPO activity.SCOPUS: re.jinfo:eu-repo/semantics/publishe