Inhibition of Ehrlich ascites cancer, hypoxia-inducible factor-1 alpha, and the kinase insert domain-containing receptor/fms-like tyrosine kinase-binding domains of vascular endothelial growth factor by Thiazole Acetamide Derivatives.

BACKGROUND: Tumor cells that have the ability to express vascular endothelial growth factor (VEGF) are more competent to growth and metastasize by the adequate amount of blood and oxygen supply by the blood vessels to the growing mass of cells. Hypoxic tumors are known for its aggressiveness and resistance to the treatment. Targeting VEGF and hypoxia-inducible factor-1 alpha (HIF-1α) is an attractive strategy to interrupt the multiple pathways crucial for tumor growth. In the present study, two thiazole acetamide derivative's anticancer property, anti VEGF and HIF-1α inhibitory property were investigated. METHODOLOGY: Two thiazole acetamide compounds were synthesized, TA1 and TA2 and its anticancer property was studied in Erlich's ascites cancer cells. To evaluate the anticancer property the assays such as 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, DNA diffusion assay for apoptosis, and lactate dehydrogenase leakage assay were carried out. The cell culture media was used to assess the secreted VEGF level. Molecular docking studies were performed to analyze the binding efficiency of the study compounds to the kinase insert domain-containing receptor (KDR) and fms-like tyrosine kinase (FLT)-binding domains of VEGF protein. HIF-1α inhibitory study was performed by flow cytometry analysis using HUVEC cell line. RESULTS: The study compounds inhibited HIF-1α and VEGF secretion, these data shown positive prop up for the anticancer property of the derivatives. The docking studies showed moderate binding of study compounds to KDR and FLT-binding domains of VEGF protein. CONCLUSION: These results conclude the anticancer and anti-angiogenic property of the synthesized thiazole-acetamide derivatives.

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.

Protective Effect of Nardostachys jatamansi Against Radiation-induced Damage at Biochemical and Chromosomal Levels in Swiss Albino Mice.

The effect of 100 mg of ethanol extract of Nardostachys jatamansi was studied on the mice exposed to 6 Gy electron beam radiation. Treatment of mice with 100 mg of Nardostachys jatamansi extract for 15 days before irradiation reduced the symptoms of radiation sickness when compared with the nondrug treated irradiated groups. The irradiation of animals resulted in an elevation in lipid peroxidation and reduction in glutathione, total antioxidants and antioxidant enzymes such as glutathione peroxidase and catalase activities. Irradiated group had shown micronucleus in the bone marrow cells. Treatment of mice with Nardostachys jatamansi extract before irradiation caused a significant depletion in lipid peroxidation followed by significant elevation in reduced glutathione, total antioxidants, glutathione peroxidase and catalase activity. It also showed a reduction in the micronucleus formation in the bone marrow cells. Our results indicate that the radioprotective activity of Nardostachys jatamansi extract may be due to free radical scavenging and increased antioxidant level in mice.

(E)-3-(3-Bromo-phen-yl)-1-(4-methyl-phenyl)prop-2-en-1-one.

The title compound, C(16)H(13)BrO, was synthesized from the reaction of 3-bromo-benzaldehyde and 4-methyl-acetophenone in the presence of KOH. The mol-ecule adopts an E configuration with respect to the C=C double bond of the propenone unit. The dihedral angle formed by the aromatic rings is 46.91 (14)°. The crystal structure is stabilized by Br⋯Br inter-actions [3.4549 (11) Å].