Santos Álvaro, Soares José Xavier, Cravo Sara, Tiritan Maria E, Reis Salette, Afonso Carlos, Fernandes Carla, Pinto Madalena M M
Laboratório de Química Orgânica e Farmacêutica, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313, Porto, Portugal.
LAQV-REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313, Porto, Portugal.
J Chromatogr B Analyt Technol Biomed Life Sci. 2018 Jan 1;1072:182-192. doi: 10.1016/j.jchromb.2017.10.018. Epub 2017 Nov 10.
For the last several years, searching of new xanthone derivatives (XDs) with potential pharmacological activities has remained one of the main areas of interest of our group. The optimization of biological activity and drug-like properties of hits and leads is crucial at early stage of the drug discovery pipeline. Lipophilicity is one of the most important drug-like properties having a great impact in both pharmacokinetics and pharmacodynamics processes. In this work, we describe the lipophilicity of a small library of bioactive XDs, previously synthesized by our group, using different methods: computational, vortex-assisted liquid-liquid microextraction coupled with high-performance liquid chromatography (VALLME-HPLC), reversed-phase high-performance thin layer chromatography (RP-HPTLC), reversed-phase high-performance liquid chromatography (RP-HPLC), and biomembrane model by the partition between micelles and aqueous phase. The different results obtained by the used methods were compared and discussed. The methodologies and data gathered in this study will expand the investigation of lipophilicity of XDs, an important class of compounds in medicinal chemistry.
在过去的几年里，寻找具有潜在药理活性的新的呫吨酮衍生物（XDs）一直是我们团队主要关注的领域之一。在药物发现流程的早期阶段，优化命中物和先导物的生物活性及类药性质至关重要。亲脂性是最重要的类药性质之一，对药代动力学和药效学过程都有很大影响。在这项工作中，我们使用不同方法描述了我们团队之前合成的一个小型生物活性XDs库的亲脂性：计算方法、涡旋辅助液液微萃取结合高效液相色谱法（VALLME-HPLC）、反相高效薄层色谱法（RP-HPTLC）、反相高效液相色谱法（RP-HPLC）以及通过胶束与水相之间的分配建立的生物膜模型。对使用这些方法获得的不同结果进行了比较和讨论。本研究中收集的方法和数据将扩展对XDs亲脂性的研究，XDs是药物化学中的一类重要化合物。
