1, 2-dithiol-3-thione and dithioester analogues: Potential radioprotectors

B. A. Teicher, J. Stemwedel, A. Rosowsky, T. S. Herman, P. K. Ghoshal

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Several l, 2-dithiol-3-thione and dithioester compounds were assayed for radioprotective capabilities in EMT6 cells in vitro. The l, 2-dithiol-3-thiones were generally more cytotoxic than the dithioesters and in some instances were more cytotoxic toward hypoxic cells than toward normally oxygenated cells. When the drugs were present at a concentration of 500 μM for 1 h prior to and during radiation delivery, the 5-(2-thienyl)-l, 2-dithiol-3-thione produced a radiation protection factor (RPF) of 2. 7 at 1 log of cell kill. The 4-methyl analogue of this same compound was, however, much less effective, producing a RPF of only 1. 2. The 4-ethoxycarbonyl analogue was moderately active, producing a RPF of 1. 7. The 4-methyl-5-(2-pyrazinyl)-dithiol-3-thione (Oltipraz) was least effective, yielding a RPF of only 1. 1. Of the dithioesters tested, methyl 3-pyrrolidino-2-phenylpropene dithiocarboxylate produced a RPF of 2. 6, methyl 3-piperidino-2- phenylpropenedithiocarboxylate a RPF of 2. 7, and the corresponding 3-morpholino and 3-thiomorpholino derivatives RPF values of 2. 7 and 2. 9, respectively. The iodide salt of 4-ethoxycarbonyl-5-(2-thienyl)-l, 2- dithiol-3-thione produced a RPF of 2. 6 Methyl 3-cyclohexylamino-2-phenylpropenedithiocarboxylate was equally effective (RPF = 2. 6). Finally, methyl 3-morpholino-3-thienyl-2-methylpropenedithiocarboxylate and methyl 3-morpholino-3-(2-pyrazinyl)-2-methylpropenedithiocarboxylate were less effective, producing RPF values of 2. 0 and 1. 6, respectively. These results demonstrate that several of these compounds are highly effective radioprotectors. In vitro and in vivo studies testing their efficacy are underway.

Original languageEnglish (US)
Pages (from-to)17-22
Number of pages6
JournalBritish Journal of Cancer
Volume62
Issue number1
DOIs
StatePublished - Jul 1990
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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