Endophytic fungi as models for the stereoselective biotransformation of thioridazine.

The stereoselective kinetic biotransformation of thioridazine, a phenothiazine neuroleptic drug, by endophytic fungi was investigated. In general, the sulfur of lateral chain (position 2) or the sulfur of phenothiazinic ring (position 5) were oxidated yielding the major human metabolites thioridazine-2-sulfoxide and thioridazine-5-sulfoxide. The quantity of metabolites biosynthesized varied among the 12 endophytic fungi evaluated. However, mono-2-sulfoxidation occurred in higher ratio and frequency. Among the 12 fungi evaluated, 4 of them deserve prominence for presenting an evidenced stereoselective biotransformation: Phomopsis sp. (TD2), Glomerella cingulata (VA1), Diaporthe phaseolorum (VR4), and Aspergillus fumigatus (VR12). Both enantiomers of thioridazine were consumed by the fungi; however, the 2-sulfoxidation yielded preferentially the R configuration at the sulfur atom.