Laboratory of Organic Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, Panepistimioupolis Zografou, 11571 Athens, Greece.
Department of Pharmacognosy and Natural Products Chemistry, Faculty of Pharmacy, National and Kapodistrian University of Athens, Panepistimiopolis Zografou, 15771 Athens, Greece.
Molecules. 2024 May 23;29(11):2458. doi: 10.3390/molecules29112458.
Thiazolin-4-ones and their derivatives represent important heterocyclic scaffolds with various applications in medicinal chemistry. For that reason, the synthesis of two 5-substituted thiazolidin-4-one derivatives was performed. Their structure assignment was conducted by NMR experiments (2D-COSY, 2D-NOESY, 2D-HSQC and 2D-HMBC) and conformational analysis was conducted through Density Functional Theory calculations and 2D-NOESY. Conformational analysis showed that these two molecules adopt conformation. Their global minimum structures have two double bonds (C=N, C=C) in Z conformation and the third double (C=N) in E. Our DFT results are in agreement with the 2D-NMR measurements. Furthermore, the reaction isomerization paths were studied via DFT to check the stability of the conformers. Finally, some potential targets were found through the SwissADME platform and docking experiments were performed. Both compounds bind strongly to five macromolecules (triazoloquinazolines, mglur3, Jak3, Danio rerio HDAC6 CD2, acetylcholinesterase) and via SwissADME it was found that these two molecules obey Lipinski's Rule of Five.
噻唑啉-4-酮及其衍生物是一类重要的杂环骨架，在药物化学中有广泛的应用。为此，我们合成了两种 5-取代的噻唑烷-4-酮衍生物。通过 NMR 实验（二维 COSY、二维 NOESY、二维 HSQC 和二维 HMBC）对其结构进行了归属，并通过密度泛函理论计算和二维 NOESY 进行了构象分析。构象分析表明，这两种分子均采用 构象。它们的全局最小结构中，两个双键（C=N，C=C）呈 Z 构象，第三个双键（C=N）呈 E 构象。我们的 DFT 结果与 2D-NMR 测量结果一致。此外，还通过 DFT 研究了反应的异构化途径，以检查构象的稳定性。最后，通过 SwissADME 平台找到了一些潜在的靶点，并进行了对接实验。这两种化合物都与五个大分子（三唑并喹唑啉、mglur3、Jak3、Danio rerio HDAC6 CD2、乙酰胆碱酯酶）结合紧密，通过 SwissADME 发现这两种分子符合 Lipinski 的五规则。
