Queuine analogues. Their synthesis and inhibition of growth of mouse L5178Y cells in vitro.
A variety of analogues of queuine (7-[(3S,4R,5S)-4,5-dihydroxycyclopent-1-en-3-ylaminomethyl]- 7 -deazaguanine), i.e., those with 7-N-substituted aminomethyl side chains and those in which the oxygen function at the 6 position of the 7-deazaguanine ring was replaced by sulfur, were synthesized and tested for ability to act as substrates for tRNA-guanine transglycosylase and for inhibitory effects on growth of mouse L5178Y leukemic cells in vitro. Of the compounds tested, analogues with sulfur at the 6 position of the 7-deazaguanine ring in place of oxygen or with an N-o-hydroxyphenyl, N-m-hydroxyphenyl, or iodoacetyl group in the 7-aminomethyl side chain in place of the naturally occurring cyclopentene diol moiety markedly inhibited the growth of cells at concentrations of 1-10 micrograms/mL, although queuine itself had practically no effect at a concentration of 100 micrograms/mL.
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D055598:Chemical Phenomena; D002621:Chemistry; D006147:Guanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism / Q000627:therapeutic use; D007940:Leukemia L5178 / Q000188:drug therapy*; D007942:Leukemia, Experimental / Q000188:drug therapy*; D051379:Mice; D010430:Pentosyltransferases / Q000378:metabolism; D012343:RNA, Transfer / Q000378:metabolism; D013329:Structure-Activity Relationship; D013455:Sulfur
D006147:Guanine; D013455:Sulfur; C019549:queuine; D012343:RNA, Transfer; D010430:Pentosyltransferases; C020837:queuine tRNA-ribosyltransferase