Omura S, Inokoshi J, Matsubara H, Tanaka H
J Antibiot (Tokyo). 1983 Dec;36(12):1709-12. doi: 10.7164/antibiotics.36.1709.
Structure-activity relationships of tylosin and related compounds were evaluated in terms of their antimicrobial and ribosome-binding activities. Demycarosyl derivatives, demycarosyltylosin and 20-deoxydemycarosylrelomycin, were slightly weaker than tylosin and 20-deoxyrelomycin, respectively, both in antimicrobial activity and in affinity to ribosomes. The corresponding demycarosyl-demycinosyl derivatives had weaker antimicrobial activities despite their relatively high affinities to ribosomes. A 23-deoxy-demycarosyl-demycinosyl derivative, 20-oxo-5-O-mycaminosylprotylonolide, had a higher affinity to ribosomes than that of tylosin and was equivalent to tylosin in antimicrobial activity against Gram-positive bacteria. These results suggest that the mycinose moiety increases the ability of the molecule to enter bacterial cells. Among the derivatives tested, a 23-iodo derivative, 20-deoxy-23-iodo-5-O-mycarosyltylonolide, had the highest affinity for ribosomes as well as the highest antimicrobial activity.
从泰乐菌素及相关化合物的抗菌活性和核糖体结合活性方面对其构效关系进行了评估。去碳霉糖基衍生物、去碳霉糖基泰乐菌素和20-脱氧去碳霉糖基瑞乐霉素在抗菌活性和对核糖体的亲和力方面分别略弱于泰乐菌素和20-脱氧瑞乐霉素。相应的去碳霉糖基-去氧胺糖基衍生物尽管对核糖体具有相对较高的亲和力，但抗菌活性较弱。一种23-脱氧-去碳霉糖基-去氧胺糖基衍生物，20-氧代-5-O- mycaminosylprotylonolide，对核糖体的亲和力高于泰乐菌素，并且在对革兰氏阳性菌的抗菌活性方面与泰乐菌素相当。这些结果表明，鼠李糖部分增加了分子进入细菌细胞的能力。在所测试的衍生物中，一种23-碘代衍生物，20-脱氧-23-碘代-5-O- mycarosyltylonolide，对核糖体具有最高的亲和力以及最高的抗菌活性。
