1. Potential radioprotective agents--VI. Chalcones, benzophenones, acid hydrazides, nitro amines and chloro compounds. Radioprotection of murine intestinal stem cells.
- Author
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Blickenstaff RT, Hanson WR, Reddy S, and Witt R
- Subjects
- Amines chemical synthesis, Amines pharmacology, Animals, Benzophenones chemical synthesis, Benzophenones pharmacology, Cell Count, Chalcone chemical synthesis, Chalcone pharmacology, Chlorides chemical synthesis, Chlorides pharmacology, Gamma Rays, Hydrazines chemical synthesis, Hydrazines pharmacology, Intestinal Mucosa cytology, Jejunum cytology, Male, Mice, Nitro Compounds chemical synthesis, Nitro Compounds pharmacology, Radiation-Protective Agents chemical synthesis, Stem Cells, Structure-Activity Relationship, Intestinal Mucosa radiation effects, Radiation-Protective Agents pharmacology
- Abstract
There is an interest and need for new compounds that protect tissues from radiation injury. In cancer therapy, the protection of normal tissue without protecting tumors is one way to increase the therapeutic gain. Thiol compounds are currently in clinical trials, but are limited to some extent by their human toxicities including hypotension, nausea, and emesis. Several new aminochalcones and aminobenzophenones were synthesized and tested for radioprotective activity in mice. All were less active than p-aminobenzophenone itself. Several acid hydrazides were synthesized and tested similarly, but none exhibited significant activity. The high radioprotective activity of 4-nitroaniline was confirmed, but other nitro amines were substantially less active. 4-Chloro-N-methylaniline is as active as 4-chloroaniline, but other chloro aromatics are devoid of significant activity. When compared with the phosphorothioate amyfostine (WR-2721) using the intestinal clonogenic cell survival assay, 1-(p-aminophenyl)-1-propanol (15), p-aminopropiophenone (16), its ethylene ketal (14), and a mixture of the two (17) protected to a great extent, though slightly less than WR-2721. These results suggest that there is direct cellular radioprotection by these non-thiol compounds. The studies further suggest that preclinical toxicity testing of the most protective agents is warranted.
- Published
- 1995
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