Kawka Anna, Nowak Damian, Koenig Hanna, Pospieszny Tomasz
Department of Bioactive Products, Faculty of Chemistry, Adam Mickiewicz University, Uniwersytetu Poznańskiego 8 Street, 61-614 Poznań, Poland.
Department of Quantum Chemistry, Faculty of Chemistry, Adam Mickiewicz University, Uniwersytetu Poznańskiego 8 Street, 61-614 Poznań, Poland.
ACS Omega. 2024 Aug 29;9(36):37995-38014. doi: 10.1021/acsomega.4c04800. eCollection 2024 Sep 10.
Molecules originating from natural sources are physicochemically and biologically diverse. The conjugation of two active biomolecules has become the foundation for medical and pharmaceutical sciences. An effective synthesis of 11 new steroid-pyrimidine conjugates containing 1,2,3-triazole rings was carried out. The group of 3α-OH bile acids (lithocholic, deoxycholic, cholic) and 3β-OH sterols (cholesterol, cholestanol) were respectively modified to azidoacetates. 2-thiouracil was converted into N(1)S and N(3)S dipropargyl derivatives. Azide-alkyne cycloaddition in the presence of copper(I) of the obtained compounds led to the preparation of 1,2,3-triazole derivatives. Based on a series of spectroscopic (H NMR, C NMR, Fourier-transform infrared (FT-IR)), spectrometric analyses (Electrospray ionization-mass spectrometry (ESI-MS), electron impact-mass spectrometry (EI-MS)), and semiempirical calculations, the structures of all compounds were confirmed. biological tests and molecular docking (for domain 1KZN, 2H94, 5V5Z, 1EZF, 2Q85) were performed for selected compounds. The tests performed indicate the theoretical antimicrobial potential of the obtained ligands.
源自天然来源的分子在物理化学和生物学性质上具有多样性。两种活性生物分子的共轭已成为医学和制药科学的基础。成功合成了11种含1,2,3 - 三唑环的新型甾体 - 嘧啶共轭物。分别将3α - OH胆汁酸（石胆酸、脱氧胆酸、胆酸）和3β - OH甾醇（胆固醇、胆甾烷醇）基团修饰为叠氮乙酸酯。将2 - 硫尿嘧啶转化为N(1)S和N(3)S二炔丙基衍生物。所得化合物在铜(I)存在下进行叠氮 - 炔环加成反应，制备出1,2,3 - 三唑衍生物。基于一系列光谱分析（氢核磁共振（H NMR）、碳核磁共振（C NMR）、傅里叶变换红外光谱（FT - IR））、质谱分析（电喷雾电离质谱（ESI - MS）、电子轰击质谱（EI - MS））以及半经验计算，确定了所有化合物的结构。对选定化合物进行了生物学测试和分子对接（针对结构域1KZN、2H94、5V5Z、1EZF、2Q85）。所进行的测试表明了所得配体的理论抗菌潜力。
