Document Detail

Design and synthesis of tryptophan containing dipeptide derivatives as formyl peptide receptor 1 antagonist.
MedLine Citation:
PMID:  23629449     Owner:  NLM     Status:  Publisher    
Our previous studies identified an Fmoc-(S,R)-tryptophan-containing dipeptide derivative, , which selectively inhibited neutrophil elastase release induced by formyl-l-methionyl-l-leucyl-l-phenylalanine (FMLP) in human neutrophils. In an attempt to improve pharmacological activity, a series of tryptophan-containing dipeptides were synthesized and their pharmacological activities were investigated in human neutrophils. Of these, five compounds , , , , and exhibited potent and dual inhibitory effects on FMLP-induced superoxide anion (O2˙(-)) generation and neutrophil elastase release in neutrophils with IC50 values of 0.23/0.60, 1.88/2.47, 1.87/3.60, 0.12/0.37, and 1.32/1.03 μM, respectively. Further studies indicated that inhibition of superoxide production in human neutrophils by these dipeptides was associated with the selective inhibition of formyl peptide receptor 1 (FPR1). Furthermore, the results of structure-activity relationship studies concluded that the fragment N-benzoyl-Trp-Phe-OMe () was most suitable as a core structure for interaction with FPR1, and may be approved as a lead for the development of new drugs in the treatment of neutrophilic inflammatory diseases. As some of the synthesized compounds exhibited separable conformational isomers, and showed diverse bioactivities, the conformation analysis of these compounds is also discussed herein.
Tsong-Long Hwang; Chih-Hao Hung; Ching-Yun Hsu; Yin-Ting Huang; Yu-Chi Tsai; Pei-Wen Hsieh
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-4-30
Journal Detail:
Title:  Organic & biomolecular chemistry     Volume:  -     ISSN:  1477-0539     ISO Abbreviation:  Org. Biomol. Chem.     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-4-30     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101154995     Medline TA:  Org Biomol Chem     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Graduate Institute of Natural Products, School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan.
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