P1,P3 Truncated Analogs of Oscillarin and their Inhibitory Activity against Blood Coagulation Factors
Authors: Hanessiana, Stephen1; Guillemette, Sébastien; Ersmark, Karolina
Source: CHIMIA International Journal for Chemistry, Volume 61, Number 6, June 2007 , pp. 361-367(7)
Publisher: Swiss Chemical Society
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.Keywords: AERUGINOSIN MIMICS; SULFONAMIDE; THROMBIN INHIBITION
Document Type: Research article
DOI: 10.2533/chimia.2007.361
Affiliations: 1: 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

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