azaserine and Carcinoma--Ehrlich-Tumor

Topics: Adenocarcinoma; Amino Sugars; Animals; Antibiotics, Antineoplastic; Azaserine; Benzazepines; Bleomycin; Carcinoma, Ehrlich Tumor; Carcinoma, Hepatocellular; Cricetinae; Dactinomycin; Daunorubicin; DNA; Dogs; Glycosides; Haplorhini; Humans; Leukemia L1210; Liver Neoplasms; Lymphoma; Mice; Mitomycins; Naphthacenes; Plicamycin; Pyrroles; Rats; RNA; Sarcoma 180; Streptonigrin; Streptozocin

Topics: Animals; Anti-Bacterial Agents; Antineoplastic Agents; Azaguanine; Azaserine; Carcinoma, Ehrlich Tumor; DNA; DNA, Neoplasm; Floxuridine; Fluorouracil; Folic Acid; Glutamine; Leukemia L1210; Mercaptopurine; Methotrexate; Mitomycin; Neoplasms; Neoplasms, Experimental; Pharmacology; Purines; Puromycin; Pyrimidines; Research; RNA; RNA, Neoplasm; Thioguanine; Thiouracil

Based on our earlier QSAR study, a series of 1, 5-N,N'-substituted-2-(substituted naphthalenesulphonyl) glutamamides were synthesized as possible anticancer agents. Anticancer activities of these synthesized compounds were evaluated in vivo on Swiss Albino mice against Ehrlich Ascites Carcinoma (EAC) cells where inhibitions of tumor cell and tumor weight were considered as biological activity parameters. A comparative QSAR study was done with a set of descriptors and logarithm of tumor cell inhibition. The result shows the importance of topological parameters like ETSA and RTSA indices as well as electronic parameter like Wang-Ford charges of different atoms. Electrophilic attack at atom number 5 and increased number of chlorine atom may be favorable whereas presence of methoxy group at the atom number 8 in naphthalene ring may be detrimental to the activity.

Topics: Animals; Antineoplastic Agents; Carcinoma, Ehrlich Tumor; Cell Line, Tumor; Cell Proliferation; Drug Screening Assays, Antitumor; Female; Glutamine; Male; Mice; Models, Molecular; Molecular Structure; Neoplasm Transplantation; Neoplasms, Experimental; Quantitative Structure-Activity Relationship; Stereoisomerism; Structure-Activity Relationship

Based on our earlier QSAR prediction, a series of designed QSAR analogs of 1,5-N,N'-disubstituted-2-(substituted benzenesulphonyl) glutamamides were synthesized as possible anticancer agents. Inhibitions of tumor cell proliferation of the compounds were tested in tumor cell line IMR-32. Anticancer activities of these compounds were also evaluated on Swiss Albino mice against Ehrlich Ascites Carcinoma (EAC) cells. Tumor weight inhibition and tumor cell inhibition were considered as anticancer activity parameters. QSAR analysis of these compounds was performed on the basis of a set of descriptors like physicochemical, topological, quantum chemical and DRAGON whole molecular descriptors. The study showed that the increase of length of substituent at R(2) position and the increase of dipole moment of the molecule decrease the anticancer activity of these compounds, presence of bromine atom at R(3) position and hydrophilic substitution at R(2) position are advantageous to the activity. Nucleophilic attack at atom number 14 is advantageous and electrophilic attack at atom number 15 is detrimental to anticancer activity. Atom number 2 is important and may be involved in dispersive interactions of the compounds with enzymes. The results offer an opportunity for further tailoring of these analogs for an active member.

Topics: Amides; Animals; Antineoplastic Agents; Carcinoma, Ehrlich Tumor; Cell Line, Tumor; Cell Proliferation; Drug Screening Assays, Antitumor; Glutamates; Humans; Mice; Quantitative Structure-Activity Relationship; Tumor Burden

The effects of lowered intracellular ATP and GTP concentrations on enzymes of purine ribonucleotide synthesis and intercoversion were studied using intact Ehrlich ascites tumor cells. The apparent rates of phosphoribosyl pyrophosphate synthetase (EC 2.7.6.1) and of inosinate dehydrogenase (EC 1.2.1.14) were increased in cells containing lowered purine nucleotide concentrations, but apparent activities of amidophosphoribosyltransferase (EC 2.4.2.14), the purine phosphoribosyltransferases, and other enzymes of purine ribonucleotide interconversion were not affected.

Topics: Adenine Phosphoribosyltransferase; Amidophosphoribosyltransferase; Animals; Antibiotics, Antineoplastic; Azaserine; Carcinoma, Ehrlich Tumor; Formaldehyde; Glycine; Hypoxanthine Phosphoribosyltransferase; Mice; Mycophenolic Acid; Phosphoribosyl Pyrophosphate; Purine Nucleotides; Ribose-Phosphate Pyrophosphokinase; Ribosemonophosphates

Amino acid starvation of Ehrlich ascites cells leads to a significant decrease of the intracellular ATP concentration concomitant with a marked decrease in nucleolar RNA polymerase activity. Addition of 8-bromoguanosine 3':5'-monophosphate (br8cGMP) to the amino-acid-deficient culture medium increased the cellular ATP levels and restored the rRNA synthesis capacity of nucleoli to control levels. Exogenous br8cAMP overcame the effects of br8cGMP. Administration of br8cAMP to exponentially growing ascites cells resulted in a shrinkage of ATP levels and in an inhibition of nucleolar RNA synthesis similar to that observed under shift-down conditions. These effects of br8cAMP could be antagonized by exogenous br8cGMP or hypoxanthine. Since the br8cGMP-induced increase in the total adenine nucleotides was abolished in the presence of azaserine (an inhibitor of the amidation of formylglycineamide ribonucleotide) it is concluded that cyclic nucleotides exert at least a part of their regulatory effects on cell proliferation by regulating nucleotide biosynthesis de novo.

Topics: Adenosine Triphosphate; Animals; Azaserine; Carcinoma, Ehrlich Tumor; Cell Line; Cell Nucleolus; Guanosine Triphosphate; Nucleotides, Cyclic; Purine Nucleosides; RNA, Ribosomal; RNA, Transfer

Topics: Animals; Azaserine; Carcinoma, Ehrlich Tumor; Cell Adhesion; Cell Aggregation; Cells, Cultured; Chick Embryo; Culture Media; Cytological Techniques; Glutamine; Indicators and Reagents; Liver Neoplasms; Mice; Norleucine; Retina; Sarcoma 180; Time Factors; Trypsin

Topics: Amides; Animals; Azaserine; Azo Compounds; Carcinoma, Ehrlich Tumor; DNA Nucleotidyltransferases; DNA, Neoplasm; Glycine; Male; Mice; Neoplasm Proteins; Neoplasm Transplantation; Templates, Genetic; Thymidine; Thymidine Kinase; Thymine Nucleotides; Time Factors; Transplantation, Homologous; Tritium

Topics: Animals; Azaserine; Carcinoma, Ehrlich Tumor; Diazooxonorleucine; Glutamine; Glycine; Kinetics; Ligases; Osmolar Concentration; Parabens; Pentosephosphates; Protein Binding

Topics: Amino Acids; Aminobutyrates; Animals; Asparaginase; Azaserine; Body Weight; Carcinoma 256, Walker; Carcinoma, Ehrlich Tumor; Drug Synergism; Excitatory Amino Acid Antagonists; Female; Glutamine; Hexoses; Male; Melanoma; Mice; Neoplasms, Experimental; Rats

Topics: Adenine; Animals; Azaserine; Carbon Isotopes; Carcinoma, Ehrlich Tumor; Cell-Free System; Cytosine Nucleotides; Electrophoresis; Glucose; Glutamine; Nucleosides; Nucleotides; Phosphorus Isotopes; Phosphotransferases; Ribose; RNA, Neoplasm; Uracil; Uridine

Topics: Animals; Antineoplastic Agents; Azaserine; Busulfan; Carcinoma, Ehrlich Tumor; Colchicine; Culture Techniques; Cyclophosphamide; Depression, Chemical; Diethylstilbestrol; Hydrazines; Immunosuppressive Agents; Mercaptopurine; Methotrexate; Thiotepa; Triaziquone; Urethane

Topics: Adenine; Animals; Antifungal Agents; Antiviral Agents; Aspartic Acid; Azaserine; Carbon Isotopes; Carcinoma, Ehrlich Tumor; Depression, Chemical; Formates; Glutamine; Glycine; Guanine; Leucine; Nitrosamines; Nucleotides; Propionates; RNA, Neoplasm; Thymidine; Tritium; Uridine

Topics: Abnormalities, Drug-Induced; Animals; Azaserine; Carcinoma, Ehrlich Tumor; DNA, Neoplasm; Female; Glucosyltransferases; Leukemia L1210; Mammary Neoplasms, Experimental; Mercaptopurine; Mice; Nucleosides; Oxidoreductases; Phosphotransferases; Pregnancy; Pregnancy, Animal; Sarcoma 180; Sarcoma, Experimental

Topics: Amides; Animals; Antimetabolites; Azaserine; Carcinoma, Ehrlich Tumor; Cycloserine; Glutamates; Male; Mice; Purines

Topics: Animals; Azaserine; Carcinoma, Ehrlich Tumor; Mercaptopurine; Mice; Purines; Pyrimidines

Topics: Adenocarcinoma; Animals; Antineoplastic Agents; Azaserine; Carcinoma 256, Walker; Carcinoma, Ehrlich Tumor; Diet; Drug Synergism; Female; Leukemia, Experimental; Lymphoma, Non-Hodgkin; Mice; Neoplasms, Experimental; Osteosarcoma; Sarcoma 180; Sarcoma, Experimental; Thiosemicarbazones; Vitamin B 6 Deficiency

Topics: Ammonia; Animals; Azaserine; Bicarbonates; Carbamates; Carcinoma, Ehrlich Tumor; Glucose; Glutamine; In Vitro Techniques; Orotic Acid; Phosphates; Serine; Uracil; Uracil Nucleotides

Topics: Amides; Animals; Azaserine; Azides; Carcinoma, Ehrlich Tumor; Diazooxonorleucine; Glutamine; Hydroxamic Acids; In Vitro Techniques; Isoleucine; Lymphoma, Non-Hodgkin; Methionine; Methionine Sulfoximine; Neoplasm Proteins; Sarcoma, Experimental; Valine

Topics: Alkylating Agents; Animals; Antimetabolites; Antineoplastic Agents; Ascites; Azaserine; Carcinoma, Ehrlich Tumor; Cyclophosphamide; Fluorouracil; Leukemia L1210; Leukemia, Experimental; Methotrexate; Mice; Neoplasms; Neoplasms, Experimental; Nitrogen Mustard Compounds; Pharmacology; Research; Thioguanine; Thiotepa; Toxicology

Topics: Adenine Nucleotides; Animals; Ascites; Azaserine; Carcinoma; Carcinoma, Ehrlich Tumor; Chromatography; Histocytochemistry; Mercaptopurine; Metabolism; Mice; Neoplasms, Experimental; Nucleotides; Pharmacology; Phosphoric Monoester Hydrolases; Research

Topics: Alkylating Agents; Animals; Antineoplastic Agents; Azaguanine; Azaserine; Carcinoma, Ehrlich Tumor; Carcinoma, Hepatocellular; DNA; DNA, Neoplasm; Fluorouracil; Idoxuridine; Liver Neoplasms; Lymphoma; Lymphoma, Non-Hodgkin; Mercaptopurine; Mice; Neoplasms, Experimental; Nitrogen Mustard Compounds; Nucleosides; Nucleotides; Purines; Research; RNA; RNA, Neoplasm; Sarcoma 180; Thioguanine; Uracil Mustard

Topics: Adenine; Adenine Nucleotides; Animals; Antineoplastic Agents; Azaserine; Carcinoma, Ehrlich Tumor; DNA; DNA, Neoplasm; Glycine; Metabolism; Mice; Nucleic Acids; Proteins; Purines; Research; RNA; RNA, Neoplasm; Thioguanine

Topics: Animals; Antineoplastic Agents; Ascites; Azaserine; Carcinoma, Ehrlich Tumor; Humans; Mercaptopurine; Neoplasms, Experimental; Pyrimidines; Thioguanine

Topics: Animals; Ascites; Azaserine; Azoles; Carcinoma, Ehrlich Tumor; Humans; Mercaptopurine; Neoplasms; Neoplasms, Experimental; Pyrimidines; Serine; Thioguanine

Topics: Animals; Antineoplastic Agents; Azaserine; Carcinoma, Ehrlich Tumor; Cell Death; DNA; Histones; Humans

Topics: Animals; Antineoplastic Agents; Azaserine; Biochemical Phenomena; Carcinoma, Ehrlich Tumor; Diploidy; Leucine; Neoplasms; RNA

Topics: Animals; Antineoplastic Agents; Azaserine; Carcinoma, Ehrlich Tumor; Deoxyribose; DNA; Neoplasms; Nucleic Acids; Proteins; Serine

Topics: Animals; Anti-Bacterial Agents; Ascites; Azaserine; Carcinoma, Ehrlich Tumor; Mercaptopurine; Neoplasms; Purines