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首页> 外文期刊>European Journal of Medicinal Chemistry: Chimie Therapeutique >Structure-activity relationships for dipeptide prodrugs of acyclovir: implications for prodrug design.
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Structure-activity relationships for dipeptide prodrugs of acyclovir: implications for prodrug design.

机译：阿昔洛韦二肽前药的构效关系：对前药设计的启示。

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摘要

A series of water-soluble dipeptide ester prodrugs of the antiviral acyclovir (ACV) were evaluated for their chemical stability, cytotoxicity, and antiviral activity against several strains of Herpes Simplex-1 and -2, vaccinia, vesicular stomatitis, cytomegalovirus and varicella zoster viruses. ACV dipeptide esters were very active against herpetic viruses, independently of the rate at which they liberate the parent drug. Their minimum cytotoxic concentrations were above 100 microM and the resulting MCC/EC(50) values were lower than those of ACV. When comparing the reactivity of Phe-Gly esters and amides (ACV, zidovudine, paracetamol, captopril and primaquine) in pH 7.4 buffer it was found that the rate of drug release increases with drug's leaving group ability. Release of the parent drug from Phe-Gly in human plasma is markedly faster than in pH 7.4 buffer, thus suggesting that the dipeptide-based prodrug approach can be successfully applied to bioactive agents containing thiol, phenol and amine functional groups.
机译：评估了一系列抗病毒阿昔洛韦（ACV）的水溶性二肽酯前药的化学稳定性，细胞毒性以及对几种单纯疱疹-1型，-2型，牛痘，水疱性口腔炎，巨细胞病毒和水痘带状疱疹病毒的抗病毒活性。 ACV二肽酯对疱疹病毒非常有效，与它们释放母体药物的速率无关。它们的最低细胞毒性浓度高于100 microM，并且产生的MCC / EC（50）值低于ACV。在pH 7.4缓冲液中比较Phe-Gly酯和酰胺（ACV，齐多夫定，对乙酰氨基酚，卡托普利和伯氨喹）的反应性时，发现药物释放速率随药物离去基团能力的增加而增加。母体药物在人血浆中从Phe-Gly释放的速度明显比在pH 7.4缓冲液中释放快，因此表明基于二肽的前药方法可以成功地应用于包含硫醇，苯酚和胺官能团的生物活性剂。

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