Jump to main content
Jump to site search

Issue 22, 2013
Previous Article Next Article

Design and synthesis of tryptophan containing dipeptide derivatives as formylpeptide receptor 1 antagonist

Author affiliations

Abstract

Our previous studies identified an Fmoc-(S,R)-tryptophan-containing dipeptide derivative, 1, 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 3, 6, 19a, 24a, and 24b 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 (3) 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.

Graphical abstract: Design and synthesis of tryptophan containing dipeptide derivatives as formyl peptide receptor 1 antagonist

Back to tab navigation

Supplementary files

Article information


Submitted
31 Jan 2013
Accepted
10 Apr 2013
First published
11 Apr 2013

Org. Biomol. Chem., 2013,11, 3742-3755
Article type
Paper

Design and synthesis of tryptophan containing dipeptide derivatives as formyl peptide receptor 1 antagonist

T. Hwang, C. Hung, C. Hsu, Y. Huang, Y. Tsai and P. Hsieh, Org. Biomol. Chem., 2013, 11, 3742
DOI: 10.1039/C3OB40215K

Social activity

Search articles by author

Spotlight

Advertisements