Abstract In this study, lipophilicity of five newly designed molecules with antibiofilm properties was estimated for the first time. The overall goal of lipophilicity evaluation in lead generation phase is to decrease the traditionally high attrition rates for compounds entering clinical trials. Lipophilicity was assessed using RP-HPLC and in silico methods. Chromatographic analyses were performed on BDS Thermo Scientific Hypersil C18 and Phenomenex Kinetex C8 columns with mobile phase consisting of acetonitrile and 20 mmol/L ammonium-acetate solution in different ratios. Retention data was used to derivatize the lipophilicity estimates and Computational substructure-based and property-based methods were employed to calculate the logP, logD, milogP, AlogP, XlogP2, XlogP3, AlogPs, AClogP and MlogP descriptors. Due to the incongruent trends of increasing hydrophobicity observed among the scales, the Sum of Ranking Differences was used to fairly evaluate the prediction ability of each method. This test unambiguously recognized AlogP and XlogP2 as the best lipophilicity measures. By virtue of the respective scales, compound denoted as DIRL PIP was identified as the most lipophilic one. Out of concern related to the DIRL PIP’s anticipated toxicity, less hydrophobic MHK 9a should be subjected to the further drug development. Graphical Abstract

中文翻译：

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新型抗生物膜剂的色谱和计算亲脂性评估

摘要 在这项研究中，首次评估了五种新设计的具有抗生物膜特性的分子的亲脂性。铅生成阶段亲脂性评估的总体目标是降低进入临床试验的化合物传统上的高损耗率。使用RP-HPLC和计算机方法评估亲脂性。色谱分析在 BDS Thermo Scientific Hypersil C18 和 Phenomenex Kinetex C8 色谱柱上进行，流动相由不同比例的乙腈和 20 mmol/L 乙酸铵溶液组成。保留数据用于推导亲脂性估计值，并采用基于计算子结构和基于特性的方法来计算 logP、logD、milogP、AlogP、XlogP2、XlogP3、AlogPs、AClogP 和 MlogP 描述符。由于在尺度之间观察到的疏水性增加的趋势不一致，因此使用排名差异总和来公平地评估每种方法的预测能力。该测试明确承认 AlogP 和 XlogP2 是最好的亲脂性措施。凭借各自的尺度，表示为 DIRL PIP 的化合物被确定为最亲脂的一种。出于对 DIRL PIP 预期毒性的关注，疏水性较低的 MHK 9a 应进行进一步的药物开发。图形概要 表示为 DIRL PIP 的化合物被确定为最亲脂的一种。出于对 DIRL PIP 预期毒性的关注，疏水性较低的 MHK 9a 应进行进一步的药物开发。图形概要 表示为 DIRL PIP 的化合物被确定为最亲脂的一种。出于对 DIRL PIP 预期毒性的关注，疏水性较低的 MHK 9a 应进行进一步的药物开发。图形概要