jm0700823_si_001.pdf (149.34 kB)
Synthesis and Pharmacological Evaluation of a Selected Library of New Potential Anti-inflammatory Agents Bearing the γ-Hydroxybutenolide Scaffold: a New Class of Inhibitors of Prostanoid Production through the Selective Modulation of Microsomal Prostaglandin E Synthase-1 Expression
journal contribution
posted on 2007-05-03, 00:00 authored by Maria D. Guerrero, Maurizio Aquino, Ines Bruno, María C. Terencio, Miguel Paya, Raffaele Riccio, Luigi Gomez-PalomaAs a part of our drug discovery effort, recently we clarified the molecular basis of phospholipase A2 (PLA2)
inactivation by petrosaspongiolide M (PM), an interesting metabolite belonging to a marine sesterterpene
family, containing in its structural architecture a γ-hydroxybutenolide moiety and showing potent anti-inflammatory activity. In the attempt to expand structural diversity as well as to simplify crucial synthetic
features of the parent compound, we decided to develop a selected library based on the densely functionalized
γ-hydroxybutenolide scaffold. The synthesized products were tested for their ability to inhibit PLA2 enzymes
as well as to modulate the expression of inducible cyclooxygenase 2 (COX-2) and microsomal prostaglandin
E synthase 1 (mPGES-1), two key enzymes highly involved in the inflammatory event, in order to discover
new promising anti-inflammatory agents with better pharmacological profiles. This led us to the discovery
of a promising inhibitor (4e) of prostanoid production acting by in vitro and in vivo selective modulation
of microsomal prostaglandin E synthase 1 expression.
History
Usage metrics
Categories
Keywords
hydroxybutenolidemarine sesterterpene familyparent compoundSelected LibrarySynthesiprostaglandin E synthase 1 expressionmetaboliteAgentprostanoid productioninducible cyclooxygenase 2profilePharmacological Evaluationfunctionalizedvivopetrosaspongiolide Mphospholipasescaffoldmodulationdrug discovery effortPMPLA 2 enzymesabilityNew ClassmPGESCOXScaffoldmoietybasisdiversityInhibitorBearingMicrosomal Prostaglandin E SynthaseinhibitoragentHydroxybutenolideinactivationProstanoid ProductionSelective ModulationExpressionAprostaglandin E synthase 1
Licence
Exports
RefWorks
BibTeX
Ref. manager
Endnote
DataCite
NLM
DC