title: Antibacterial nitroacridine, Nitroakridin 3582: binding to nucleic acids in vitro and effects on selected cell-free model systems of macromolecular biosynthesis.
abstract: Nitroakridin 3582 (NA) formed complexes with native deoxyribonucleic acid (DNA) and with transfer ribonucleic acid (tRNA) species from Escherichia coli. Spectrophotometric titrations of NA with these nucleic acids produced numerical results from which nonlinear adsorption isotherms were derived. These curves indicated the existence of more than one class of binding sites on the polymers to which NA was bound by more than one process. The stoichiometry of strong binding of NA to double helical DNA was in agreement with a conventional value (1 ligand molecule per 4.2 component nucleotides) for complete intercalation binding. NA inhibited the DNA-dependent DNA polymerase I and RNA polymerase reactions, the first strongly and the second appreciably. These inhibitions corresponded to the extents to which NA inhibits DNA and RNA biosyntheses in vivo. Evidently, NA interferes with the template function of DNA. The drug also inhibited the polymerization of phenylalanine in a cell-free E. coli ribosome-polyuridylic acid [poly (U)] system. The effect paralleled an inhibition of the poly (U)-directed binding of phenylalanyl tRNA to ribosomes. Ethidium bromide acted similarly. The antimalarial drug, chloroquine, stimulated polyphenylalanine synthesis, apparently as a result of stimulating the poly (U)-directed binding of phenylalanyl tRNA to ribosomes.
mesh_terms: D000166:Acridines / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001665:Binding Sites; D002247:Carbon Isotopes; D002474:Cell-Free System; D002738:Chloroquine / Q000494:pharmacology; D004254:DNA Nucleotidyltransferases / Q000037:antagonists & inhibitors; D004269:DNA, Bacterial / Q000096:biosynthesis* / Q000378:metabolism; D004926:Escherichia coli / Q000187:drug effects* / Q000378:metabolism; D005827:Genetics, Microbial; D006358:Hot Temperature; D008837:Micrococcus / Q000201:enzymology; D008956:Models, Chemical; D009574:Nitro Compounds / Q000494:pharmacology; D009691:Nucleic Acid Denaturation; D009696:Nucleic Acids / Q000378:metabolism*; D010617:Phenanthridines / Q000494:pharmacology; D010649:Phenylalanine / Q000096:biosynthesis / Q000378:metabolism; D011119:Polynucleotides / Q000378:metabolism; D011485:Protein Binding; D011796:Quinacrine / Q000494:pharmacology; D012316:RNA Nucleotidyltransferases / Q000037:antagonists & inhibitors; D012329:RNA, Bacterial / Q000096:biosynthesis*; D012343:RNA, Transfer / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism; D013053:Spectrophotometry; D013698:Templates, Genetic; D014316:Tritium
chemical_list: D000166:Acridines; D000900:Anti-Bacterial Agents; D002247:Carbon Isotopes; D004269:DNA, Bacterial; D009574:Nitro Compounds; D009696:Nucleic Acids; D010617:Phenanthridines; D011119:Polynucleotides; D012329:RNA, Bacterial; D014316:Tritium; D010649:Phenylalanine; D002738:Chloroquine; D012343:RNA, Transfer; D004254:DNA Nucleotidyltransferases; D012316:RNA Nucleotidyltransferases; D011796:Quinacrine