TOXICITY OF 2 PAIRS OF EPIMERIC IONOPHOROUS ANTIBIOTICS TOWARDS TETRAHYMENA-PYRIFORMIS - STRUCTURE-ACTIVITY RELATIONSHIP

Structure-activity relationship of four ionophorous antibiotics, niger icin (C-29-CH2OH) and grisorixin (C-29-CH3) and their respective epime rs, epinigericin and epigrisorixin where the methyl is in axial positi on on C-28, was investigated. Toxicity studies of these antibiotics (1 0 mg/l) were carried out with respect to the population time course of . T. pyriformis in the exponential growth phase, and DNA and RNA synth esis. Results showed different durations of cell division inhibition w hich increased in the following order: epigrisorixin < epinigericin < grisorixin < nigericin. All four antibiotics caused a marked decrease in DNA and RNA synthesis at the beginning of the experiment. For each pair, nigericin and grisorixin were more active than their respective epimers (epinigericin and epigrisorixin). Toxicity differences towards Tetrahymena, between nigericin/grisorixin and between each antibiotic and its epimer, may be due respectively to structural differences at carbons 30 and 28.