P1,P3 Truncated Analogs of Oscillarin and their Inhibitory Activity against Blood Coagulation Factors

Authors

  • Stephen Hanessiana Department of Chemistry, Université de Montréal, P.O. Box 6128, Station Centre-ville, Montréal, QC, H3C 3J7, Canada, Tel: +1 514 343 6738, Fax: +1 514 343 5728, Email: stephen.hanessian@umontreal.ca
  • Sébastien Guillemette
  • Karolina Ersmark

DOI:

https://doi.org/10.2533/chimia.2007.361

Keywords:

Aeruginosin mimics, Sulfonamide, Thrombin inhibition

Abstract

Based on modeling and available X-ray co-crystal structure data of oscillarin with the enzyme thrombin, a series of P1,P3 truncated analogs were prepared using the azabicyclic octahydroindole carboxamide core as a scaffold. The P1 subunit of the original natural product was replaced by a 4-amidinobenzamide group, and the P3 subunit was simulated by N-benzylsulfonyl glycine amide or an N-acetyl D-phenylalanine amide. Single digit micromolar inhibition was found against trypsin, thrombin, Factor Xa, and Factor XIa for some analogs.

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Published

2007-06-27

Issue

Vol. 61 No. 6 (2007): Natural Products in Drug Discovery

Section

Scientific Articles

License

Copyright (c) 2007 Swiss Chemical Society

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

How to Cite

[1]
S. Hanessiana, S. Guillemette, K. Ersmark, Chimia 2007, 61, 361, DOI: 10.2533/chimia.2007.361.