Abstract—Potential FXa inhibitors were developed by a
rational design in the first instance, focusing on a key
pharmacophore, present in gold standard drugs Rivaroxaban
and Apixaban. The phenyl lactam scaffold filling one of the
subsites in the catalytic site, S4 pocket, with significant aromatic
π-π stacking interactions, allows this frame to be invariably
located with accuracy, because of the six membered lactam ring
attached to an aromatic benzene ring. We anticipated that the
addition of an alkyne unit would enable the exploration of the
first section of S1 pocket, in this way producing a better
molecule optimizing binding between our potential inhibitor
and the active site of FXa. A fluorimetric assay was performed
to determine IC50 values on the proposed molecules. All these
findings were rationalized by docking energy delta and
theoretical structure, vibrational and reactivity analysis to
formulate a more accurate explanation about which structure
has is the optimal inhibitor for this therapeutic target in the
blood coagulation cascade.
Index Terms—FXa inhibitors, molecular docking, theoretical
calculations, in vitro fluorimetric assay, synthetic inhibitors,
anticoagulants.
F. S. Romo is with Pontificia Universidad Católica de Chile, Faculty of
Chemistry and Pharmacy, Santiago, Chile (e-mail: fmsantana@uc.cl).
Y. Duarte is with Center for Bioinformatics and Integrative Biology,
Facultad de Ciencias de la Vida, Universidad Andrés Bello, Santiago, Chile
(e-mail: yorley.duarte@unab.cl).
F. Castillo is with Institute for Biological and Medical Engineering,
Schools of Engineering, Medicine and Biological Sciences, Pontificia
Universidad Católica de Chile, Santiago, Chile (e-mail: fjcastil@uc.cl).
M. A. Maestro is with Department of Chemistry—CICA, University of A
Coruña, Campus da Zapateira, A Coruña, Spain (e-mail:
miguel.maestro@udc.es).
F. C. Zacconi is with Faculty of Chemistry and Pharmacy; Institute for
Biological and Medical Engineering, Schools of Engineering, Medicine and
Biological Sciences, and Research Center for Nanotechnology and
Advanced Materials (CIEN-UC), Pontificia Universidad Católica de Chile,
Santiago de Chile, Chile (e-mail: fzacconi@uc.cl).
[PDF]
Cite: Fabián Santana-Romo, Yorley Duarte, Francisco Castillo, Miguel A. Maestro, and Flavia C. Zacconi, "Microwave-Mediated Synthesis of N-allyl/Propargyl Derivatives: Enzymatic Analysis as a Potential Factor Xa (FXa) Inhibitor, Theoretical and Computational Molecular Docking," International Journal of Chemical Engineering
and Applications vol. 11, no. 1, pp. 34-41, 2020.
