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

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 for sulphur mustard (SM; a blistering agent) toxicity. When given orally, DRDE-07 was more effective than amifostine as a prophylactic agent against SM administered percutaneously. Various pharmacological and toxicological studies are required before the introduction of a chemical as a drug. The respiratory effects of amifostine and DRDE-07 were carried out in rats using a body plethysmograph fitted with a volumetric pressure transducer for sensing the respiratory flow signals. The signals were amplified, digitised, and stored on a personal computer for further analysis. After taking control recordings of respiratory signals, different doses (0.5 LD50, 1.0 LD50 and 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 and DRDE-07 showed a uniform breathing pattern even in 2.0 LD50 dose. However, a significant dose-dependent decrease in respiratory frequency was observed following amifostine administration. DRDE-07 did not show any significant change. The tidal volume was not altered significantly both in amifostine and DRDE-07 administered animals. The study shows that DRDE-07, even in lethal doses, may not affect the respiration immediately, whereas, amifostine may decrease the respiratory frequency

Catalyst-Controlled Structural Divergence: Selective Intramolecular 7-<i>endo</i>-<i>dig</i> and 6-<i>exo</i>-<i>dig</i> Post-Ugi Cyclization for the Synthesis of Benzoxazepinones and Benzoxazinones

Metal catalyzed post-Ugi cyclization of bis-amides is reported in this study. Exposure of bis-amides to Pd­(II) catalyst triggered the formation of seven-membered benzoxazepinones. This investigation established that changing the catalyst to a Echavarren’s gold­(I) turned off cyclization to seven member ring and turned on 6-<i>exo</i>-<i>dig</i> annulations to afford family of six-membered benzoxazinones. To support the proposed mechanisms, quantum chemical based density functional theory calculations have been performed and validated. This novel method obtained molecular complexity up to four modular inputs and divergence of two different skeletons. 2D NMR spectroscopic techniques and single crystal X-ray diffraction established the proposed structures