Inhibitors of N^α-acetyl-l-ornithine Deacetylase: Synthesis, Characterization and Analysis of their Inhibitory Potency

Authors

J. Hlavacek, Academy of Sciences of the Czech RepublicFollow
J. Picha, Academy of Sciences of the Czech Republic
V. Vanek, Academy of Sciences of the Czech Republic
J. Jiracek, Academy of Sciences of the Czech RepublicFollow
J. Slaninova, Academy of Sciences of the Czech Republic
V. Fucik, Academy of Sciences of the Czech Republic
M. Budesinsky, Academy of Sciences of the Czech RepublicFollow
Danuta M. Gillner, Loyola University Chicago
Richard C. Holz, Marquette University

Document Type

Article

Publication Date

4-2010

Source Publication

Amino Acids

Source ISSN

0939-4451

Abstract

A series of N ^α-acyl (alkyl)- and N ^α-alkoxycarbonyl-derivatives of l- and d-ornithine were prepared, characterized, and analyzed for their potency toward the bacterial enzyme N ^α-acetyl-l-ornithine deacetylase (ArgE). ArgE catalyzes the conversion of N ^α-acetyl-l-ornithine to l-ornithine in the fifth step of the biosynthetic pathway for arginine, a necessary step for bacterial growth. Most of the compounds tested provided IC₅₀ values in the μM range toward ArgE, indicating that they are moderately strong inhibitors. N ^α-chloroacetyl-l-ornithine (1g) was the best inhibitor tested toward ArgE providing an IC₅₀ value of 85 μM while N ^α-trifluoroacetyl-l-ornithine (1f), N ^α-ethoxycarbonyl-l-ornithine (2b), and N ^α-acetyl-d-ornithine (1a) weakly inhibited ArgE activity providing IC₅₀ values between 200 and 410 μM. Weak inhibitory potency toward Bacillus subtilis-168 for N ^α-acetyl-d-ornithine (1a) and N ^α-fluoro- (1f), N ^α-chloro- (1g), N ^α-dichloro- (1h), and N ^α-trichloroacetyl-ornithine (1i) was also observed. These data correlate well with the IC₅₀ values determined for ArgE, suggesting that these compounds might be capable of getting across the cell membrane and that ArgE is likely the bacterial enzymatic target.

Comments

Accepted version. Amino Acids. Vol. 38, No. 4 (April 2010): 1155-1164. DOI. © 2010 Springer Nature Switzerland AG. Part of Springer Nature. Used with permission.

Richard C. Holz was affiliated with Loyola University-Chicago at the time of publication.

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Recommended Citation

Hlavacek, J.; Picha, J.; Vanek, V.; Jiracek, J.; Slaninova, J.; Fucik, V.; Budesinsky, M.; Gillner, Danuta M.; and Holz, Richard C., "Inhibitors of N^α-acetyl-l-ornithine Deacetylase: Synthesis, Characterization and Analysis of their Inhibitory Potency" (2010). Chemistry Faculty Research and Publications. 287.
https://epublications.marquette.edu/chem_fac/287