A simple microbiological assay for the stereospecific differentiation of ? and ? isomers of arteether

A new rapid bioassay has been developed which can precisely differentiate between stereospecific alpha and beta isomers of the antimalarial drug arteether. This method was developed through the disc diffusion bioactivity tests wherein semisynthetically produced alpha arteether was able to inhibit the growth of E. coli strains which are defective in DNA gyrase enzyme. The wild type E. coli with intact DNA gyrase did not show this sensitivity to alpha arteether. The beta isomer of arteether was, however, ineffective against both the mutant and wild type strains. Direct experimental proof of gyrase involvement was obtained through mobilization of gyr genes by transformation of E. coli gyr- mutant strains with wild type gyrA clone pMK90 (carried on the thermo-inducible lambda Col E1 vector). This resulted in alpha arteether resistant and nalidixic acid sensitive phenotype clearly demonstrating the use of gyrA mutant strains in differentiating alpha and beta isomers of arteether by this simple bioassay.