Werner R G, Lechner U L, Goeth H
Antimicrob Agents Chemother. 1982 Jan;21(1):101-6. doi: 10.1128/AAC.21.1.101.
A number of alkyl and acyl derivatives of 4-dihydro-4-deoxy-4(R)-amino spectinomycin were tested against various Escherichia coli strains, possessing different susceptibilities to spectinomycin. The influence of the lipophilicity and the length of the side chain substituents of the derivatives was compared to both minimal inhibitory concentration values and stability to adenyltransferase. Derivatives with a chain length of more than 10 carbon atoms demonstrated a significantly higher activity against all investigated strains, whether susceptible or resistant. The same inhibitory effect was achieved with short-chain aminoacyl derivatives only against susceptible strains. Other short-chain derivatives possessed no advantage to spectinomycin. A 10-fold decrease in the affinity for adenyltransferase was achieved in compounds with a high lipophilicity (log P), i.e., in aliphatic substituted derivatives with a log P greater than 4 and in benzoyl-substituted derivatives with a log P greater than 2. Derivatives with branched alkyl chains and long side chains displayed a different mode of action than spectinomycin. They possessed strong activity against strains with an altered ribosomal binding site and a decreased influence of pH on antimicrobial activity.
对4-二氢-4-脱氧-4(R)-氨基壮观霉素的多种烷基和酰基衍生物针对不同的大肠杆菌菌株进行了测试，这些菌株对壮观霉素具有不同的敏感性。将衍生物的亲脂性和侧链取代基的长度对最低抑菌浓度值和对腺苷酸转移酶的稳定性的影响进行了比较。链长超过10个碳原子的衍生物对所有研究菌株（无论是敏感菌株还是耐药菌株）均表现出显著更高的活性。短链氨基酰基衍生物仅对敏感菌株具有相同的抑制作用。其他短链衍生物相对于壮观霉素没有优势。亲脂性（log P）高的化合物，即log P大于4的脂肪族取代衍生物和log P大于2的苯甲酰基取代衍生物，对腺苷酸转移酶的亲和力降低了10倍。具有支链烷基链和长侧链的衍生物表现出与壮观霉素不同的作用方式。它们对核糖体结合位点改变的菌株具有强大活性，且pH对抗菌活性的影响降低。
