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 thioridazine5- 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.