Sulindac oxidation/reduction by microbial cultures; microbial models of mammalian metabolism

The oxidation and reduction of the sulphoxide moiety of the anti-inflammatory agent sulindac was investigated to explore microbial systems exhibiting parallels of known mammalian metabolism. Of 24 cultures initially screened, four catalysed the expected reactions in analytical studies. Arthrobacter species (ATCC 19140) and Sporobolomyces pararoseus (ATCC 11386) produced sulindac sulphide, Aspergillus alliaceus (NRRL 315) produced sulindac sulphone, and Nocardia corallina (ATCC 19070) produced both the sulphide and sulphone. Preparative-scale production and full structural elucidation of metabolites was accomplished for sulindac sulphide with Arthrobacter species, and sulindac sulphone with A. alliaceus and N. corallina. N. corallina also exhibited an aeration-dependent, reversible reduction of sulindac to the sulphide, and further oxidation to the sulphone. This organism thus parallels the composite of major phase-I redox transformations of this drug observed in mammals.