3-Cyclic amine derivatives of rifamycin: strong inhibitors of the DNA polymerase activity of RNA tumor viruses.
Derivatives of rifamycin-SV with substituted cyclic-amine side chains in position 3 of the ansa ring are strong inhibitors of RNA-directed DNA and DNA-directed DNA polymerase activity of RNA tumor viruses of murine, feline, and avian origin. Among 37 3-amine derivatives of rifamycin-SV that were tested, 29 3-cyclic amine derivatives were good inhibitors of the viral polymerases. Especially active were 3-piperidyl derivatives of rifamycin-SV with cyclohexyl and cyclohexylalkyl substituents. Derivatives that were effective against the viral polymerase also blocked cell transformation by the murine sarcoma virus. A DNA-directed DNA polymerase preparation from human KB cells was less sensitive to inhibition by these derivatives than the virion polymerase.
D000818:Animals; D001354:Avian Leukosis Virus / Q000187:drug effects / Q000201:enzymology; D002415:Cats; D004254:DNA Nucleotidyltransferases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004279:DNA, Viral / Q000378:metabolism; D003864:Depression, Chemical; D017988:Gammaretrovirus / Q000187:drug effects / Q000201:enzymology; D008979:Moloney murine leukemia virus / Q000187:drug effects / Q000201:enzymology; D012316:RNA Nucleotidyltransferases / Q000037:antagonists & inhibitors; D012328:RNA Viruses / Q000187:drug effects / Q000201:enzymology*; D012367:RNA, Viral / Q000378:metabolism; D012190:Retroviridae / Q000187:drug effects / Q000201:enzymology; D012293:Rifampin / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013942:Thymine Nucleotides / Q000378:metabolism; D014316:Tritium
D004279:DNA, Viral; D012367:RNA, Viral; D013942:Thymine Nucleotides; D014316:Tritium; D004254:DNA Nucleotidyltransferases; D012316:RNA Nucleotidyltransferases; D012293:Rifampin