Hydroxyurea Derivatives

Summary

1-Hydroxybiuret (1-HB) and 3-hydroxybiuret (3-HB) were shown to be inhibitors of DNA synthesis in an in vitro Ehrlich ascites tumor test system in NCTC-109 medium. Inhibition was manifest almost immediately upon addition of either compound to the cells. The rates of synthesis of RNA and protein were not substantially altered by either compound. Removal of each inhibitor by washing the cells did not completely restore the rate of DNA synthesis to its control value. The inhibitory action of each against DNA synthesis was antagonized by a mixture of deoxyribosides, suggesting that inhibition of ribonucleotide bioreduction may be a major mode of action, similar to that of hydroxyurea. Morphological evidence indicated that 3-HB induced unbalanced growth in several strains of Pseudomonas, but 1-HB was devoid of activity in the microbial system.