Interruption of oncornavirus replication by modified rifamycin antibiotics.
Thirteen rifamycin SV derivatives containing 3'-alkylaminomethyl substituents fail to inhibit the activities of the simian sarcoma virus Type 1 DNA polymerase, and of cellular DNA, RNA, and poly(A) polymerases prepared from NIH Swiss mouse embryos. These compounds show a range in their toxicities for NIH Swiss mouse 3T3 cells and in their capacities to inhibit production of foci of morphologically altered cells by murine sarcoma virus (MSV). Three compounds--the N-methyl-N-hydroxyethylaminomethyl, the N,N-dimethyl-aminomethyl, and the N4-methylpiperazinomethyl rifamycin derivatives--are comparable to adenine arabinoside and ribavirin in their toxicity for 3T3 cells, but these compounds show superior focus inhibition. These compounds inhibit oncornavirus production apparently by exacerbation of a delay in growth that results from infection of 3T3 cells with MSV.
D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D012321:DNA-Directed RNA Polymerases / Q000037:antagonists & inhibitors; D019384:Nucleic Acid Synthesis Inhibitors; D011062:Polynucleotide Adenylyltransferase / Q000037:antagonists & inhibitors; D012190:Retroviridae / Q000187:drug effects*; D018894:Reverse Transcriptase Inhibitors; D012294:Rifamycins / Q000494:pharmacology*; D012842:Sarcoma Virus, Woolly Monkey / Q000187:drug effects / Q000201:enzymology; D009053:Sarcoma Viruses, Murine / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects*
D019384:Nucleic Acid Synthesis Inhibitors; D018894:Reverse Transcriptase Inhibitors; D012294:Rifamycins; D011062:Polynucleotide Adenylyltransferase; D012321:DNA-Directed RNA Polymerases