The influence of double bond geometry in the inhibition of cyclooxygenases by sulindac derivatives.
Basic Information
ID: ALA1158428
Journal: Bioorg Med Chem Lett
Title: The influence of double bond geometry in the inhibition of cyclooxygenases by sulindac derivatives.
Authors: Walters MJ, Blobaum AL, Kingsley PJ, Felts AS, Sulikowski GA, Marnett LJ.
Abstract: Sulindac sulfide is a benzylidene-indene that is a potent, time-dependent inhibitor of cyclooxygenases-1 and -2. Removal of the 2'-methyl group from the indene ring dramatically reduces time-dependent inhibition of both enzymes but also changes the geometry of the benzylidene double bond from Z to E. Herein, we explore the importance of double bond geometry on cyclooxygenase inhibition. The Z-isomer of 2'-des-methyl sulindac sulfide was synthesized by reduction of a bromoindene precursor or by photoisomerization of the E-isomer. The Z-isomer inhibited both cyclooxygenases, but with diminished potency compared to sulindac sulfide. Thus, although the 2'-methyl group is a major determinant of time-dependent cyclooxygenase inhibition, the geometry of the benzylidene double bond plays a role as well.
CiteXplore: 19427206
DOI: 10.1016/j.bmcl.2009.04.078
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