ABSTRACT
An environmentally benign, simple, efficient, and convenient route is described for the synthesis of novel pyrazolo[1,5-a]pyrimidine derivatives under ultrasound irradiation. Condensation of aminopyrazole 5 with formylated active proton compounds (6, 8, E-G, 12, and 15) furnished pyrazolopyrimidine (7, 9, 10, 13, and 16) in high-to-excellent yields. In comparison with conventional methods, ultrasound irradiation offers several advantages, such as shorter reaction time, higher yields, milder conditions, and environmental friendliness. The reaction is clean with excellent yields and reduces the use of solvents. X-ray crystallographic study of compound 7c confirmed the regioselectivity of the reaction. The antibacterial profile of the newly synthesized compounds was evaluated by cup and saucer method.
Subject(s)
Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/pharmacology , Pyrimidines/chemical synthesis , Pyrimidines/pharmacology , Sulfates/chemistry , Ultrasonic Waves , Water/chemistry , Anti-Bacterial Agents/chemistry , Bacteria/drug effects , Chemistry Techniques, Synthetic , Pyrimidines/chemistry , StereoisomerismABSTRACT
An attempt was made to evaluate the whole body gamma-radiation effect on tumor in the presence of free and liposome encapsulated AK-2123, a hypoxic cell radiosensitizer that has widely been used in combination with a number of cancer therapies such as thermotherapy, chemotherapy and radiotherapy. Entrapment efficiency of AK-2123 into liposome was determined by LASER Raman spectroscopy. Cancer induction in mice was carried out by repeated exposure of N-nitrosodiethylamine (DEN) in combination with partial hepatectomy. Parameters such as marker enzymes activities (GGT and AChE), rates of nucleic acid synthesis, viability modification factor and the histology of liver tissues monitored, supported the induction of cancer in liver. In addition, the effect of free as well as liposome encapsulated AK-2123 on haemopoietic parameters were also studied. It was observed that AK-2123 after incorporation into liposome afforded more efficient radiomodulatory effects than that of free AK-2123 as determined by the above-mentioned parameters. Neither free AK-2123 nor liposome encapsulated AK-2123 showed any detectable toxic effects on the mice. Thus, it is seen that treatment of cancer with a combination of radiation, a radiomodifier and a drug delivery system, opens a wide scope for exploitation for the improvement of existing cancer therapies.
Subject(s)
Liposomes/pharmacology , Liver Neoplasms/drug therapy , Radiation-Sensitizing Agents/pharmacology , Triazoles/pharmacology , Acetylcholinesterase/drug effects , Acetylcholinesterase/metabolism , Acetylcholinesterase/radiation effects , Animals , Carcinogens/toxicity , Combined Modality Therapy , DNA/biosynthesis , DNA/drug effects , DNA/radiation effects , Diethylnitrosamine/toxicity , Gamma Rays , Liver Neoplasms/chemically induced , Liver Neoplasms/pathology , Liver Neoplasms/radiotherapy , Male , Mice , Mice, Inbred BALB C , RNA/biosynthesis , RNA/drug effects , RNA/radiation effects , Whole-Body Irradiation , gamma-Glutamyltransferase/drug effects , gamma-Glutamyltransferase/metabolism , gamma-Glutamyltransferase/radiation effectsABSTRACT
The present investigation is aimed to identify and characterize tumor-associated antigen (TAA) in animals exposed to hepatocarcinogen. Swiss albino mice showed an enhanced expression of an approximately 58 kDa glycoprotein in liver cells upon exposure to a potential hepatocarcinogen N-nitrosodibutylamine (DBN). Carcinogenesis induction in mice was monitored by assays of y-glutamyl transpeptidase (GGT), acetylcholine esterase (AChE), glutathione-S-transferase (GST) activities and the level of glutathione (GSH) in liver. DBN treated animals showed cell distortion and extensive necrosis as observed by histological examination. The over-expressed TAA was purified by ion-exchange chromatography and further characterized by SDS-PAGE. The carbohydrate contents and glycan linkage to the polypeptide backbone was analyzed by using the DIG glycan differentiation and de-glycosylation kits. The glycoprotein has glycan chains that are N-linked via asparagines to the polypeptide backbone. It was also observed that the molecule is rich in sialic acid residues with a significantly high carbohydrate to protein ratio (> 2:1). The over-expressed high molecular weight glycoprotein TAA was found to be highly immunogenic and could eventually be used to induce immune response in order to counter tumor regression.
