Brunell, David published the artcileStudies on the metabolism and biological activity of the epimers of Sulindac, Category: naphthyridine, the publication is Drug Metabolism and Disposition (2011), 39(6), 1014-1021, database is CAplus and MEDLINE.
Sulindac is a nonsteroidal, anti-inflammatory drug (NSAID) that was also studied for its anticancer activity. Recent studies suggest that sulindac and its metabolites act by sensitizing cancer cells to oxidizing agents and drugs that affect mitochondrial function, resulting in the production of reactive oxygen species and death by apoptosis. In contrast, normal cells are not killed under these conditions and, in some instances, are protected against oxidative stress. Sulindac has a Me sulfoxide moiety with a chiral center and was used in all of the previous studies as a mixture of the R- and S-epimers. Because epimers of a compound can have very different chem. and biol. properties, we have separated the R- and S-epimers of sulindac, studied their individual metabolism, and performed preliminary experiments on their effect on normal and lung cancer cells exposed to oxidative stress. Previous results had indicated that the reduction of (S)-sulindac to sulindac sulfide, the active NSAID, was catalyzed by methionine sulfoxide reductase (Msr) A. In the present study, we purified an enzyme that reduces (R)-sulindac and resembles MsrB in its substrate specificity. The oxidation of both epimers to sulindac sulfone is catalyzed primarily by the microsomal cytochrome P 450 (P 450) system, and the individual enzymes responsible have been identified. (S)-Sulindac increases the activity of the P 450 system better than (R)-sulindac, but both epimers increase primarily the enzymes that oxidize (R)-sulindac. Both epimers can protect normal lung cells against oxidative damage and enhance the killing of lung cancer cells exposed to oxidative stress.
Drug Metabolism and Disposition published new progress about 59973-80-7. 59973-80-7 belongs to naphthyridine, auxiliary class Immunology/Inflammation,COX, name is Sulindac sulfone, and the molecular formula is C20H17FO4S, Category: naphthyridine.
Referemce:
https://en.wikipedia.org/wiki/1,8-Naphthyridine,
1,8-Naphthyridine | C8H6N2 – PubChem