Hybrids of antibiotics inhibiting protein synthesis. Synthesis and biological activity.
Four hybrid antibiotics combining structural features of chloramphenicol (1a), sparsomycin (2b), lincomycin (5c), and puromycin (6d)--lincophenicol (1c), chloramlincomycin (5a), sparsolincomycin (5b), and sparsopuromycin (6b)--were synthesized. They were investigated as inhibitors of several partial reactions of procaryotic and eucaryotic protein synthesis as well as potential antimicrobial agents. Lincophenicol (1c) was active as inhibitor of Escherichia coli ribosomal peptidyltransferase-catalyzed puromycin reaction. Both lincophenicol (1c) and sparsophenicol (1b) inhibited the binding of the iodophenol analogue of sparsomycin to E. coli ribosomes. The results are discussed in terms of a retro-inverso hypothesis advanced earlier for interpretation of biological activity of chloramphenicol (1a) and sparsophenicol (1b). Chloramlincomycin (5a) suppressed the growth of Streptococcus pyogenes with MIC 6.25 micrograms/mL.
Zemlicka
J
J
Department of Chemistry, Michigan Cancer Foundation, Detroit 48201.
Fernandez-Moyano
M C
MC
Ariatti
M
M
Zurenko
G E
GE
Grady
J E
JE
Ballesta
J P
JP
D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002701:Chloramphenicol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D004926:Escherichia coli / Q000201:enzymology; D008034:Lincomycin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D008099:Liver / Q000648:ultrastructure; D010458:Peptidyl Transferases / Q000037:antagonists & inhibitors; D014176:Protein Biosynthesis; D011500:Protein Synthesis Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D011691:Puromycin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D011744:Pyrimidinones / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D012270:Ribosomes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D013033:Sparsomycin / Q000378:metabolism; D013297:Streptococcus pyogenes / Q000187:drug effects
D000900:Anti-Bacterial Agents; D011500:Protein Synthesis Inhibitors; D011744:Pyrimidinones; C081113:lincophenicol; C081114:chloramlincomycin; C081115:sparsolincomycin; C081116:sparsopuromycin; D011691:Puromycin; D002701:Chloramphenicol; D013033:Sparsomycin; D008034:Lincomycin; D010458:Peptidyl Transferases