Department of Organic Chemistry, Faculty of Pharmaceutical Sciences in Sosnowiec, The Medical University of SilesiaJagiellońska 4, 41-200 Sosnowiec, Poland.
Doctoral School, The Medical University of Silesia, 40-055 Katowice, Poland.
Int J Mol Sci. 2023 Apr 9;24(8):6970. doi: 10.3390/ijms24086970.
Lipophilicity is one of the key properties of a potential drug that determines the solubility, the ability to penetrate through cell barriers, and transport to the molecular target. It affects pharmacokinetic processes such as adsorption, distribution, metabolism, excretion (ADME). The 10-substituted 1,9-diazaphenothiazines show promising if not impressive in vitro anticancer potential, which is associated with the activation of the mitochondrial apoptosis pathway connected with to induction BAX, forming a channel in MOMP and releasing cytochrome c for the activation of caspases 9 and 3. In this publication, the lipophilicity of previously obtained 1,9-diazaphenothiazines was determined theoretically using various computer programs and experimentally using reverse-phase thin-layer chromatography (RP-TLC) and a standard curve. The study presents other physicochemical, pharmacokinetic, and toxicological properties affecting the bioavailability of the test compounds. ADME analysis was determined in silico using the SwissADME server. Molecular targets studies were identified in silico using the SwissTargetPrediction server. Lipinski's rule of five, Ghose's, and Veber's rules were checked for the tested compounds, confirming their bioavailability.
亲脂性是潜在药物的关键性质之一，决定了药物的溶解度、穿透细胞屏障的能力以及向分子靶标的输送。它影响药物动力学过程，如吸收、分布、代谢和排泄（ADME）。10 位取代的 1,9-二氮杂苯并噻嗪类化合物具有有前途的体外抗癌潜力，这与线粒体凋亡途径的激活有关，与诱导 BAX 有关，形成 MOMP 中的通道并释放细胞色素 c 以激活 caspase 9 和 3。在本出版物中，使用各种计算机程序从理论上和使用反相薄层色谱 (RP-TLC) 和标准曲线从实验上确定了先前获得的 1,9-二氮杂苯并噻嗪类化合物的亲脂性。该研究还介绍了影响测试化合物生物利用度的其他物理化学、药代动力学和毒理学特性。使用 SwissADME 服务器在计算机上进行 ADME 分析。使用 SwissTargetPrediction 服务器在计算机上进行分子靶标研究。检查了受试化合物是否符合 Lipinski 的五规则、Ghose 规则和 Veber 规则，以确认其生物利用度。
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