Structural modification of polyfunctional rubratoxin B: effects on mammalian adenosine triphosphatase. Academic Article uri icon


  • Rubratoxin B, an alpha, beta unsaturated lactone containing bisanhydride metabolite of certain toxigenic strains of penicillium molds, significantly inhibited in vitro brain microsomal Na+ - K+ adenosine triphosphatase from swine, mouse, and rat with IC50's of 6.76, 6.67, and 6.80 x 10(-6) M, respectively. Mitochondrial Mg++ oligomycin-sensitive ATPase from mouse liver was also inhibited with an IC50 of 6.30 x 10(-6) M rubratoxin B. Structural modification of the polyfunctional parent compound (rubratoxin B) to rubratoxin A (a gamma lactol replaces one of the anhydride moieties) or formation of the dihydro analogs of rubratoxins A and B (2,3 saturated delta lactone) decreased inhibition to all ATPase systems. The structure-activity relationship relative to ATPase inhibition was rubratoxin B greater than dihydrorubratoxin B greater than rubratoxin A greater than dihydrorubratoxin A. The order of reactivity by these analogs to brain microsomal Na+ -K+ ATPase from 3 mammalian species and to mouse hepatic mitochondrial Mg++ ATPase was similar, indicating no significant species variations. These results suggest that the previously demonstrated in vivo inhibition of adenosine triphosphatase preparations by rubratoxin B was the result of the intact parent compound, because chemical alteration of any one of the functional moieties (either the maleic anhydride ring or conjugated lactone) resulted in significantly decreased inhibition of ATPase activity.

author list (cited authors)

  • Phillips, T. D., & Hayes, A. W.

citation count

  • 8

complete list of authors

  • Phillips, TD||Hayes, AW

publication date

  • January 1979