Acyloxybutadiene tricarbonyl iron complexes as enzyme-triggered CO-releasing molecules (ET-CORMs): a structure-activity relationship study.
A series of η(4)-acyloxycyclohexadiene-Fe(CO)(3) complexes was prepared and fully characterized by spectroscopic methods including single crystal X-ray diffraction. For this purpose a new synthetic access to differently acylated 1,3- and 1,5-dienol-Fe(CO)(3) complexes was developed. The enzymatically triggered CO release from these compounds was monitored (detection of CO through GC and/or by means of a myoglobin assay) and the anti-inflammatory effect of the compounds was assessed by a cellular assay based on the inhibition of NO-production by inducible NO synthase (iNOS). It was demonstrated that the properties (rate of esterase-triggered CO release, iNOS inhibition, cytotoxicity) of the complexes strongly depend on the substitution pattern of the π-ligand and the nature of the acyloxy substituent.
Department für Chemie, Universität zu Köln, Germany.
Steffen
S
Romanski
Birgit
B
Kraus
Miguel
M
Guttentag
Waldemar
W
Schlundt
Hannelore
H
Rücker
Andreas
A
Adler
Jörg-Martin
JM
Neudörfl
Roger
R
Alberto
Sabine
S
Amslinger
Hans-Günther
HG
Schmalz
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D058085:Iron Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D058085:Iron Compounds; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II