@article {CONKLIN304, author = {K. A. CONKLIN and P. HEU and S. C. CHOU}, title = {The Effects of Antimalarial Drugs on Nucleic Acid Synthesis in Vitro in Tetrahymena pyriformis}, volume = {9}, number = {3}, pages = {304--310}, year = {1973}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {Solubilized DNA and RNA polymerases were prepared from disrupted nuclei of Tetrahymena pyriformis and partially purified by gel filtration on Sephadex G-100. The enzymes were characterized and shown to carry out DNA replication and DNA-dependent RNA synthesis. The effects of three antimalarial drugs, quinine, primaquine, and chloroquine, on DNA and RNA syntheses by the intact nuclei and the solubilized polymerases were also investigated. For each drug dose-response curves were constructed, with each curve including the two drug concentrations which have previously been found to inhibit cell division by 80-90\% and 100\%, respectively, in T. pyriformis. At these two concentrations quinine and primaquine were shown to have relatively little inhibitory effect on the reactions of the test systems in vitro as compared to previously reported inhibition of precursor incorporation into nucleic acids of intact cells. These results indicate that the primary action of these two drugs in T. pyriformis may not be inhibition of nucleic acid synthesis, and that they may possess another mechanism for blocking precursor incorporation by T. pyriformis in vivo. Chloroquine, however, at the concentrations which block cell division, was shown to inhibit markedly the synthesis of both DNA and RNA by the solubilized polymerases and DNA synthesis by nuclei. These results indicate that inhibition of nucleic acid synthesis may, in part, account for the effects of this drug on T. pyriformis. ACKNOWLEDGMENT The authors would like to thank Sterling-Winthrop for their generous gift of primaquine diphosphate.}, issn = {0026-895X}, URL = {https://molpharm.aspetjournals.org/content/9/3/304}, eprint = {https://molpharm.aspetjournals.org/content/9/3/304.full.pdf}, journal = {Molecular Pharmacology} }