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    • ISSN: 2010-0221 (Print)
    • Abbreviated Title: Int. J. Chem. Eng. Appl.
    • Frequency: Bimonthly
    • DOI: 10.18178/IJCEA
    • Editor-in-Chief: Prof. Dr. Shen-Ming Chen
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Editor-in-chief
Prof. Dr. Shen-Ming Chen
National Taipei University of Technology, Taiwan
 

IJCEA 2020 Vol.11(1): 34-41 ISSN: 2010-0221
doi: 10.18178/ijcea.2020.11.1.776

Microwave-Mediated Synthesis of N-allyl/Propargyl Derivatives: Enzymatic Analysis as a Potential Factor Xa (FXa) Inhibitor, Theoretical and Computational Molecular Docking

Fabián Santana-Romo, Yorley Duarte, Francisco Castillo, Miguel A. Maestro, and Flavia C. Zacconi
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).

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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.

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