Radioprotective effect of sulphydryl group containing triazole derivative to modulate the radiation- induced clastogenic effects.

Protection of biological systems against radiation damage is of paramount importance during accidental and unavoidable exposure to radiation. Several physico-chemical and biological factors collectively contribute to the damage caused by radiation and are, therefore, targets for developing radioprotectors. Chemicals capable of scavenging free radicals, relieving oxidative stress, promoting antioxidant activity and modulating immune response have been some of the radioprotectors extensively investigated with limited success. It has long been known that some of the most effective radioprotective agents are those which contain sulphydryl groups. 4-amino-5-mercapto-3-methyl-1, 2, 4-triazole (AMMT) is one of the well-known 1, 2, 4 triazole derivatives with functional sulphydryl group. The present study reports an evaluation of radical scavenging and radioprotective properties of sulphydryl group containing triazole derivative. The lethal dose of electron beam radiation (EBR) was studied by survival assay. The dose reduction factor (DRF) of AMMT was calculated using the ratio between LD50 of EBR with and without AMMT treatment. Radical scavenging property of AMMT was assessed by DPPH radical scavenging assay. The clastogenic effects of EBR were recorded by Micronucleus test in bone marrow cells and DNA fragmentation assay in mice hepatic cells. The survival assay results showed that the LD50 of EBR was 10 Gy. The calculated DRF for AMMT was found to be 1.2. DPPH radical scavenging assay showed a positive result when it was compared with the standard glutathione. Treatment of mice with 100 mg of AMMT for 15 days before irradiation significantly (P<0.05) reduced the frequency of micronucleus formation in bone marrow cells and also reduced the DNA fragmentation in hepatic cells. The results obtained in the present study indicated that AMMT has a protective effect against the EBR-induced mortality and clastogenicity.

Synthesis of some halogen-containing 1,2,4-triazolo-1,3,4-thiadiazines and their antibacterial and anticancer screening studies--part I.

A series of 7-arylidene-6-(2,4-dichloro-5-fluorophenyl)-3-substituted-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazines (3) were prepared by the condensation of 4-amino-5-mercapto-3-substituted-1,2,4-triazoles (1) and 3-aryl-1-(2,4-dichloro-5-fluorophenyl)-2-bromo-2-propen-1-one (2). An alternative route for the synthesis of the title compound 3 has been described. The newly synthesised compounds were characterised on the basis of N-analyses, IR, 1H NMR and mass spectral data. Some of the newly synthesised compounds were tested for their antibacterial activities against Gram + ve and Gram - ve bacteria. Among the tested compounds 3n showed the highest degree of antibacterial activity against S. aureus and evaluation of the LD50 value of this compound was carried out. Some of the newly synthesised compounds were also screened for their anticancer activities. Among these, compounds 3b, 3g, 3n and 3p are found to be active against NCI-H460 (lung), MCF7 (breast), SF 268 (CNS) in the preliminary anticancer screening studies. Further, 60-cell-line anticancer studies of these compounds were carried out. The results of such studies are discussed in this paper.