Nitrotriazoles bearing sulfur-substituted side chains: preparation and characterization as hypoxic cell radiosensitizers

A series of 3-nitro-1,2,4-triazole (NTA) derivatives with -(CH2)mC(= Y)NH(CH2)nZCH3(Y, Z = O or S; m = 1 or 2; n = 2 or 3) group in the side chain at the N-1 position of NTA and their fluorinated analogs were synthesized. Their physicochemical properties and radiosensitizing activities in vitro and...

Full description

Saved in:
Bibliographic Details
Published inAnti-cancer drug design Vol. 7; no. 3; p. 277
Main Authors Sugita, T, Masuoka, M, Nishikawa, Y, Nishimoto, S, Zhou, L, Sasai, K, Kagiya, T
Format Journal Article
LanguageEnglish
Published United States 01.06.1992
Subjects
Animals
Cell Hypoxia
Female
Mice
Mice, Inbred C3H
Radiation-Sensitizing Agents - chemical synthesis
Radiation-Sensitizing Agents - chemistry
Radiation-Sensitizing Agents - pharmacology
Solubility
Structure-Activity Relationship
Triazoles - chemical synthesis
Triazoles - pharmacology
Online AccessGet more information

Cover

More Information
Summary:A series of 3-nitro-1,2,4-triazole (NTA) derivatives with -(CH2)mC(= Y)NH(CH2)nZCH3(Y, Z = O or S; m = 1 or 2; n = 2 or 3) group in the side chain at the N-1 position of NTA and their fluorinated analogs were synthesized. Their physicochemical properties and radiosensitizing activities in vitro and in vivo were investigated with respect, particularly, to the effects of sulfur substitution on the side chain of triazoles. The sulfur substitution of the oxygen atom in the side chain of NTA derivatives increased the partition coefficient (P value), but had little effect on the one-electron reduction potential. The derivatives bearing a thioether group in the side chain were more effective in vitro on hypoxic EMT6/KU cells, but were less effective in vivo on SCCVII tumor than their oxygen analogs. The thioamide compounds showed almost the same or slightly higher sensitizing activities in vitro compared with their oxygen analogs.
ISSN:0266-9536