Zemlicka J, Fernandez-Moyano M C, Ariatti M, Zurenko G E, Grady J E, Ballesta J P
Department of Chemistry, Michigan Cancer Foundation, Detroit 48201.
J Med Chem. 1993 Apr 30;36(9):1239-44. doi: 10.1021/jm00061a015.
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.
合成了四种结合氯霉素（1a）、稀疏霉素（2b）、林可霉素（5c）和嘌呤霉素（6d）结构特征的杂合抗生素——林可苯甲酰氯霉素（1c）、氯林可霉素（5a）、稀疏林可霉素（5b）和稀疏嘌呤霉素（6b）。它们被作为原核生物和真核生物蛋白质合成的几种部分反应的抑制剂以及潜在的抗菌剂进行了研究。林可苯甲酰氯霉素（1c）作为大肠杆菌核糖体肽基转移酶催化的嘌呤霉素反应的抑制剂具有活性。林可苯甲酰氯霉素（1c）和稀疏苯甲酰氯霉素（1b）都抑制了稀疏霉素的碘酚类似物与大肠杆菌核糖体的结合。根据先前提出的用于解释氯霉素（1a）和稀疏苯甲酰氯霉素（1b）生物活性的反向假说对结果进行了讨论。氯林可霉素（5a）抑制化脓性链球菌的生长，最低抑菌浓度为6.25微克/毫升。
