Synthesis of hydroxy- and amino-substituted benzohydroxamic acids: inhibition of ribonucleotide reductase and antitumor activity

J Med Chem. 1979 May;22(5):589-92. doi: 10.1021/jm00191a027.


Benzohydroxamic acids inhibit mammalian ribonucleotide reductase and exhibit antineoplastic activity in L1210 leukemic mice. Five new hydroxy- and amino-substituted benzohydroxamic acids (3,4- and 3,5-OH, 3,4-NH2, 2,3,4- and, 3,4,5-OH) were prepared and tested along with 12 previously reported benzohydroxamic acids (BHA) for enzyme inhibition and antitumor activity. The most potent enzyme inhibitor in this series was 2,3,4-OH-BHA (ID50 = 3.5 microM), which is 140 times more potent than hydroxyurea, but its toxicity limited the antitumor activity to a 30% increase in life span of L1210 bearing mice at 125 (mg/kg)/day ip for 8 days. The most effective antitumor agent in this series was 3,4-OH-BHA which prolonged the life span of L1210 bearing mice 103% at 600 (mg/kg)/day ip for 8 days.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis*
  • Dose-Response Relationship, Drug
  • Female
  • Hydroxamic Acids / chemical synthesis*
  • Hydroxamic Acids / pharmacology
  • Hydroxamic Acids / therapeutic use
  • Hydroxyurea / therapeutic use
  • In Vitro Techniques
  • Leukemia L1210 / drug therapy
  • Liver Neoplasms, Experimental / enzymology
  • Mice
  • Ribonucleotide Reductases / antagonists & inhibitors*
  • Structure-Activity Relationship


  • Antineoplastic Agents
  • Hydroxamic Acids
  • Ribonucleotide Reductases
  • Hydroxyurea