Radiosensitization by quaternary salts of 5-nitroimidazole derivatives.
The radiosensitizing effects of five newly synthesized quaternary salts of 5-nitroimidazole derivatives on the survival of TC-SV40 mammalian cells have been measured. A toxicity study was carried out in order to determine the concentrations to be used in the radiosensitizing experiments. The oxygen enhancement ratio (OER) for TC-SV40 cells was 2.74. None of the five 5-nitroimidazole derivatives showed radiosensitizing activity in aerobic conditions, while in hypoxia their dose-modifying factors (DMF) at the concentration of 0.2 mmol dm-3 range from 1.52 to 1.03 in this order: unsubstituted pyridinium greater than carbamoyl pyridinium greater than trimethyl pyridinium greater than t-butyl pyridinium greater than imidazolium. This latter product at the concentration of 2 mmol dm-3 has a DMF of 1.64. As comparison, metronidazole was also tested on this cell line and its DMF at 0.2 mmol dm-3 was 1.35. The response-concentration dependences for the unsubstituted pyridinium 5-nitroimidazole derivative and for metronidazole (comparing charged and uncharged structures) showed the flattening response-concentration curve of quaternary compounds. The electron affinity was evaluated through the CNDO/S theoretical method, and an exponential relationship between these values and the DMFs of the pyridinium derivatives was demonstrated.
Santos
L
L
Instituto de Quìmica Física Rocasolano, C.S.I.C., Serrano, Madrid.
Lopez Zumel
M C
MC
Alvarez
M V
MV
Izquierdo
M C
MC
D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D006224:Cricetinae; D008647:Mesocricetus; D008795:Metronidazole / Q000494:pharmacology; D009593:Nitroimidazoles / Q000494:pharmacology* / Q000633:toxicity; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology* / Q000633:toxicity
D009593:Nitroimidazoles; D011838:Radiation-Sensitizing Agents; D008795:Metronidazole; C052587:4-nitroimidazole