Back to Search
Start Over
Synthesis of hydroxy- and amino-substituted benzohydroxamic acids: inhibition of ribonucleotide reductase and antitumor activity.
- Source :
-
Journal of medicinal chemistry [J Med Chem] 1979 May; Vol. 22 (5), pp. 589-92. - Publication Year :
- 1979
-
Abstract
- 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.
- Subjects :
- Animals
Dose-Response Relationship, Drug
Female
Hydroxamic Acids pharmacology
Hydroxamic Acids therapeutic use
Hydroxyurea therapeutic use
In Vitro Techniques
Leukemia L1210 drug therapy
Liver Neoplasms, Experimental enzymology
Mice
Structure-Activity Relationship
Antineoplastic Agents chemical synthesis
Hydroxamic Acids chemical synthesis
Ribonucleotide Reductases antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 0022-2623
- Volume :
- 22
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Journal of medicinal chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 458812
- Full Text :
- https://doi.org/10.1021/jm00191a027