TY - JOUR
AU - Young, Robert, C.
AB - Abstract Forty-four rifamycin derivatives with substitutions at the 3-carbon and 4-carbon positions of the rifamycin nucleus were tested for Inhibition of 1) DNA polymerases α, β, and γ (DPα, DPβ, and DPγ, respectively) from leukemia Iymphoblasts and phytohemagglutinin-stimulated normal human lymphocytes, 2) terminal deoxynucleotldyl transferase (tdT) from leukemia Iymphoblasts, and 3) reverse transcrlptase (RT) from simian sarcoma virus. Eighteen compounds were substantially Inhibitory to different degrees. One of these, 3'-acetyl-1'-benzyl-2'-methylpyrrolo[3,2-c]-4-desoxy-rlfamycln SV (derivative PRI19), selectively Inhibited TdT, and the other 17 compounds exhibited no striking selectivity toward any of the enzymes when assayed with the use of reaction mixtures containing no added bovine serum albumin (BSA). The structure-activity relationships of these results showed that compounds with long alkyl chains (8–11 carbon atoms) at the 3-carbon position of the rifamycin nucleus were among the most potent Inhibitors. Also, the addiction of aromatic moieties to side groups at the 3-carbon position could sometimes enhance the Inhibitory potential of a series of compounds. Inhibition of DPα, DPβ, and DPγ by rifamycin derivatives was completely or partially prevented by addition of BSA to assay mixtures at concentrations of 250 μg/ml, but inhibition of TdT and RT was unaffected by It. These data suggest a greater specificity of rifamycin derivatives for TdT and RT than for DPα, DPβ, and DPγ. Furthermore, a greater specificity of rifamycin derivatives for DPα, DPβ, and DPγ than for BSA was Indicated, Inasmuch as Inhibition of those DNA polymerases by rifamycin derivatives was prevented by concentrations of BSA (250 μg/ml) that were much higher than those of enzyme protein (≤3 μg/ml). This content is only available as a PDF. Author notes 2 Environmental Epidemiology Branch, Division of Cancer Cause and Prevention, National Cancer Institute (NCI), National Institutes of Health (NIH), Public Health Service, U.S. Department of Health, Education, and Welfare, Bethesda. Md. 20014. 3 Present address: Department of Hematology and Medical Oncology, Cleveland Clinic Foundation, 9500 Euclid Ave., Cleveland, Ohio 44106. 5 Medicine Branch, Division of Cancer Treatment, NCI. 6 We thank the members of the Society of Gynecologic Oncologists whose cooperative efforts made this study possible; Dr. Max H. Myers for providing data from the End Results Program; and Ms. Terry Thomas, Ms. Nancy Jones, Ms. Wendy Cohen, Ms. Rita Feran, Mrs. Kathy Diblazio, and Ms. Diane Crouse for technical assistance.
TI - Second Primary Neoplasms Following Ovarian Cancer
JF - JNCI: Journal of the National Cancer Institute
DO - 10.1093/jnci/61.5.1195
DA - 1978-11-01
UR - https://www.deepdyve.com/lp/oxford-university-press/second-primary-neoplasms-following-ovarian-cancer-PsMw1GRmTz
SP - 1195
EP - 1197
VL - 61
IS - 5
DP - DeepDyve
ER -