Open AccessP1,P3 Truncated Analogs of Oscillarin and their Inhibitory Activity against Blood Coagulation Factors
Author(s) -
Stephen Hanessiana,
Sébastien Guillemette,
Karolina Ersmark
Publication year - 2007
Publication title -
chimia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.387
H-Index - 55
eISSN - 2673-2424
pISSN - 0009-4293
DOI - 10.2533/chimia.2007.361
Subject(s) - amide , chemistry , stereochemistry , thrombin , coagulation , phenylalanine , glycine , enzyme , carboxamide , protein subunit , trypsin , amino acid , biochemistry , platelet , biology , medicine , psychiatry , gene , immunology
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.