Around the macrolide - Impact of 3D structure of macrocycles on lipophilicity and cellular accumulation

作者：Kostrun Sanja^*; Kos Vesna Munic; Skugor Maja Matanovic; Jakopovic Ivana Palej; Malnar Ivica; Dragojevic Snjezana; Ralic Jovica; Alihodzic Sulejman

来源：European Journal of Medicinal Chemistry, 2017, 133: 351-364.

DOI：10.1016/j.ejmech.2017.03.056

• Cellular accumulation
• Lipophilicity
• 3D structures
• Statistical models

The aim of this study was to investigate lipophilicity and cellular accumulation of rationally designed azithromycin and clarithromycin derivatives at the molecular level. The effect of substitution site and substituent properties on a global physico-chemical profile and cellular accumulation of investigated compounds was studied using calculated structural parameters as well as experimentally determined lipophilicity. In silico models based on the 3D structure of molecules were generated to investigate conformational effect on studied properties and to enable prediction of lipophilicity and cellular accumulation for this class of molecules based on non-empirical parameters. The applicability of developed models was explored on a validation and test sets and compared with previously developed empirical models.

• 出版日期2017-6-16