The successful implication of the chemical weapons convention stimulated research
with a new vigour on the destruction of the stockpiled sulphur mustard (SM). A prophylactic
agent for SM will be very useful for personnel engaged in the destruction of SM and
during inspections by the Organisation for the Prohibition of Chemical Weapons. Due
to simple method of preparation, SM can be used clandestinely during war or by terrorist
groups. Inspite of research over several decades no satisfactory prophylactic or treatment
regimen has evolved for SM. Amifostine an organophosphorothioate, originally developed
as a radioprotector, and its analogues were evaluated as a prophylactic agent for
SM. Three analogues by varying the chain length and substitution at the sulphur atom
were synthesised and coded as DRDE-06, DRDE-07 and DRDE-08. LD(50) of amifostine and
its analogues were estimated through intraperitoneal (i.p.) route. For the protection
studies, amifostine and its analogues were administered i.p. in mice, 30 min before
dermal (percutaneous) application of SM. The dose of the prophylactic agent was 0.2
LD(50) (i.p.) and that of SM was 152 mg/kg (undiluted) equal to 19-fold LD(50) of
SM. Amifostine and one of its analogues, DRDE-07 gave significant protection. Further
studies were carried out using amifostine and DRDE-07, and both of them significantly
protected mice against SM (155 mg/kg, in PEG 300, equal to 19 LD(50)) when they were
administered i.p. either 30 min before or simultaneously. LD(50) of amifostine and
DRDE-07 were also estimated through the oral route (1049 or 1248 mg/kg, respectively).
Prophylactically administered amifostine and DRDE-07 (0.2 LD(50), p.o.) significantly
protected the mice against dermally applied SM (155 mg/kg, in PEG 300, equal to 19
LD(50)). The protection offered by DRDE-07 was better than that of amifostine by the
oral route. DRDE-07 (0.2 LD(50), p.o.) also protected significantly with respect to
the decrease in body weight and the depletion of GSH induced by SM. DNA damage induced
by SM was also significantly reduced by amifostine and DRDE-07 (0.2 LD(50), p.o.).
Further studies are in progress on the various pharmacological and toxicological properties
of DRDE-07.