4-phenylhydrazinocyclohex-3-en-2-oxo-6-phenyl-1-oate)—a novel enhydrazone ester, was tested in vitro for anti-inflammatory activity
against the release of pro-inflammatory cytokine and prostanoid from
lipopolysaccharide-activated human monocytes or human monocytic cell line
(U937). The effects were compared with those of standard anti-inflammatory
drugs dexamethasone and indomethacin. CEE-1 potently and strongly inhibited
the release of both tumor necrosis factor-alpha (TNF-α) and prostaglandin E2 (PGE2). The concentrations producing 50% inhibition (IC50 values) were 2.0 μM and 2.4 μM for TNF-α and PGE2, respectively. At
30 μM, the drug achieved almost complete inhibition of both mediators. Dexamethasone
had similar effects but indomethacin inhibited only the PGE2 release, and although CEE-1 was less potent than these two drugs, it had comparable efficacy. The compound appeared to act, at least, in part by inhibiting the
up-regulation of the mRNA for TNF-α as well as that of the prostanoid-synthetic
enzyme, cyclo-oxygenase-2 (COX-2). However, like dexamethasone, but unlike
indomethacin, CEE-1 did not affect COX-2 enzyme function. Thus, the profile of
activity of CEE-1 is similar to that of steroids rather than the non-steroidal
anti-inflammatory drugs. Structure-activity study showed that the presence of a
simple aromatic ring attached via an NH-NH group was critical for activity. At
the concentrations that completely inhibited mediator release, the compound displayed
no significant in vitro toxicity on
the cells. These results show that CEE-1 is a dual inhibitor of the release of
cytokines and prostanoids, and therefore could be a potential alternative to
steroids in the treatment of inflammatory diseases.
Cite this paper
Ezeamuzie, C. , Zamil, H. , Al-Baghli, H. and Edafiogho, I. (2013) Pharmacological evaluation of a novel enhydrazone ester (CEE-1) as a dual inhibitor of the release of pro-inflammatory cytokines and prostanoids from human monocytes. Advances in Bioscience and Biotechnology, 4, 54-63. doi: 10.4236/abb.2013.48A2008.
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