Prophylactic Efficacy of Amifostine, DRDE-07, and their Analogues against Percutaneously Administered Nitrogen Mustards and Sulphur Mustard

Nitrogen mustards (HN-1, HN-2 and HN-3) and sulphur mustard are alkylating and blister-inducing chemical warfare agents. This study was aimed at investigating the prophylactic efficacy of amifostine, DRDE-07, and their analogues and some recommended antidotes against dermally-applied nitrogen mustards and sulphur mustard in preventing their systemic toxicity in mice. The antidotes were administered as single oral dose, 30 min prior to the mustard agent application. For DRDE-07, 0.2 LD50 (249 mg/kg) was used and for other analogues, equimolar dose of DRDE-07 was used. For amifostine, N-acetyl cysteine, melatonin and sodium thiosulphate, oral dose was 185 mg/kg, 250 mg/kg, 250 mg/kg, and 1000 mg/kg respectively. The animals were observed for mortality for 14 days. The protection index (PI) was calculated as a ratio of LD50 with treatment to LD50 without treatment. The protection of the antidotes was also determined by intraperitoneal route and half of the oral dose of the antidotes was given. The estimated percutaneous LD50 of HN-1, HN-2, HN-3 and sulphur mustard was 11.9 mg/kg, 20.0 mg/kg, 7.1 mg/kg and 7.1 mg/kg, respectively. Compounds that showed marginal protection against HN-1 were DRDE-10 and melatonin with a PI of 1.4. Compounds that showed marginal protection against HN-2 were amifostine, DRDE-07, DRDE-09, DRDE-30, DRDE-35 and melatonin with a PI of 1.4. Compounds that showed marginal protection against HN-3 were amifostine, DRDE-30, DRDE-35, sodium thiosulphate and melatonin with a PI of 1.7. In the case of sulphur mustard, DRDE-07, DRDE-10, DRDE-21, DRDE-30, and DRDE-35 gave a good protection with a PI of more than 5.0. Amifostine and sodium thiosulphate gave a PI of 4.5 and 4.0, respectively, while DRDE-09, N-acetyl cysteine and melatonin gave less protection against sulphur mustard. Intraperitoneally administered amifostine, DRDE-30, sodium thiosulphate and melatonin gave marginal protection against HN-2 with a PI of 1.2, while intraperitoneally administered amifostine, DRDE-07, DRDE-09, DRDE-10, DRDE-30, DRDE-35 and melatonin gave excellent protection against percutaneously administered sulphur mustard with a PI of more than 5.0. The present study shows, that oral and intraperitoneal administration of amifostine, DRDE-07 and their analogues are effective as prophylactic agents for sulphur mustard systemic toxicity, but not against nitrogen mustards.Defence Science Journal, 2009, 59(5), pp.512-516, DOI:http://dx.doi.org/10.14429/dsj.59.155

Respiratory Effects of Amifostine and DRDE-07: Probable Prophylactic Agents of Sulphur Mustard in Rats

Amifostine (S-2[3-aminopropylamino]ethyl phosphorothioate) and one of its analogues,DRDE-07 (S-2[2-aminoethylamino]ethyl phenyl sulphide) are promising prophylactic agents forsulphur mustard (SM; a blistering agent) toxicity. When given orally, DRDE-07 was more effectivethan amifostine as a prophylactic agent against SM administered percutaneously. Variouspharmacological and toxicological studies are required before the introduction of a chemical asa drug. The respiratory effects of amifostine and DRDE-07 were carried out in rats using a bodyplethysmograph fitted with a volumetric pressure transducer for sensing the respiratory flowsignals. The signals were amplified, digitised, and stored on a personal computer for furtheranalysis. After taking control recordings of respiratory signals, different doses (0.5 LD50, 1.0 LD50and 2.0 LD50) of amifostine and DRDE-07 were administered orally (LD50 amifostine = 2262 mg/kg; DRDE-07 = 1599 mg/kg), and the respiratory changes were monitored for 4 h. Amifostine andDRDE-07 showed a uniform breathing pattern even in 2.0 LD50 dose. However, a significant dosedependentdecrease in respiratory frequency was observed following amifostine administration.DRDE-07 did not show any significant change. The tidal volume was not altered significantlyboth in amifostine and DRDE-07 administered animals. The study shows that DRDE-07, even inlethal doses, may not affect the respiration immediately, whereas, amifostine may decrease therespiratory frequency

Pigeonpea nutrition and its improvement

Pigeonpea (Cajanus cajan [L.] Millsp.), known by several vernacular and names such as red gram, tuar, Angola pea. yellow dhal and oil dhal, is one of the major grain legume crops of the tropics and sub-tropics. It is a crop of small holder dryland fmmers because it can grow well under subsistence level of agriculture and provides nutritive food, fodder, and fuel wood. It also improves soil by fixing atmospheric nitrogen. India by far is the largest pigeonpea producer it is consumed as decorticated split peas, popularly called as 'dhaL' In other countries, its consumption as whole dty and green vegetable is popular. Its foliage is used as fodder and milling by-products [onn an excellent feed for domestic animals. Pigeonpea seeds contain about 20-22% protein and appreciable amounts of essential amino.acids and minerals. DehuHing and boiling treatments of seeds get rid of the most antinutritional factors as tannins and enzyme inhibitors. Seed storage causes considerable losses in the quality of this legume. The seed protein of pigeonpea has been successfully enhanced by breeding from 20-22% to 28-30%. Such lines also agronomically performed well and have acceptable and color. The high-protein lines were found nutritionally superior to the cultivars because they would provide more quantities of utilizable protein and sulfur-containing amino acids

A facile and efficient microwave-mediated <i>S</i>-alkylation of thiophosphates

602-605A convenient, highly efficient, safe microwave-mediated S-alkylation of O,O’-dialkyl thiophosphate has been reported. Clean and rapid S-alkylation of thiophosphates can be achieved by irradiating a mixture of dialkylthiophosphate salt and alkyl halide under microwave for a brief period. Alkylation occurs exclusively at sulfur to provide S-alkylated products. Through a simple workup, pure compounds have been obtained easily in good yields.</i

Analgesic and anti-inflammatory activity of amifostine, DRDE-07, and their analogs, in mice

Objectives : To find out the analgesic and anti-inflammatory activity, if any, of Amifostine [S-2(3 amino propyl amino) ethyl phosphorothioate], DRDE-07 [S-2(3 amino ethyl amino) ethyl phenyl sulphide] and their analogs DRDE-30 and DRDE-35, the probable prophylactic agent for sulphur mustard (SM). Materials and Methods : In order to find out the analgesic activities of the compounds two methods were employed, namely, acetic acid-induced writhing test and formalin-induced paw licking. The persistent pain model of formalin-induced hind paw licking was carried out to test the effect of the compounds on neurogenic pain or early phase (0 to 5 minutes) and on the peripheral pain or the late phase (15 to 30 minutes). To test the effect of the compound in acute inflammation, carrageenan-induced hind paw edema was carried out. This model of inflammation involves a variety of mediators of inflammation. Results : DRDE-07 (81.7%) and DRDE-30 (79.4%) showed significant reduction in the acetic acid-induced writhing test. DRDE-07 (93.1%), DRDE-30 (82%), and DRDE-35 (61.3%) showed significant reduction in the second or late phase of formalin-induced paw licking. All the analogs (more than 60%) including amifostine (43.9%) showed significant reduction of paw edema in the carrageenan-induced paw edema in mice. Conclusion : The analgesic and anti-inflammatory activity of the antidotes were comparable with aspirin

A convenient one-pot preparation of <i style="">N</i>-substituted thioamides

1225-1228A convenient one-pot preparation of N-substituted thioamides from acyl halides, amines and H2O/PSCl3/Et3N in good to excellent yield has been reported through a solvent-free, microwave assisted method

Amifostine: An Effective Prophylactic Agent against Sulphur Mustard Toxicity (Short Communication)

Amifostine, S-2-(aminopropylamino) ethylphosphorothioate and two of its analogues have been evaluated as prophylactic agent against SM toxicity. The compounds were administered intraperitoncally (i.p.) at 0.2 LD/sub59 dose in mice 30 min prior to dermal application of SM. The protective efficacy was determined by observing the mortality for 14 days. The protection offered by amifostine was better than its analogues. Subsequent study on time-dependent protection, carried out with amifostine (0.2 LD/sub50, i.p.) provided significant protection when the drug was administered as 30 min pre-treatment and simultaneous treatment against SM at 155 mg.kg/-1 dose (equal to 19-fold LD/sub50). Furthermore, oral administration of amifostine (30 min pre-treatment) showed similar results. These findings suggest that amifostine is a promising prophylactic agent against SM toxicity