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

2017; Elsevier BV; Volume: 133; Linguagem: Inglês

10.1016/j.ejmech.2017.03.056

1768-3254

Sanja Koštrun, Vesna Munić Kos, Maja Matanović Škugor, Ivana Palej Jakopović, Ivica Malnar, Snježana Dragojević, Jovica Ralić, Sulejman Alihodžić,

Bioactive Compounds and Antitumor Agents

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.