Kahriman Nuran, Peker Kıvanç, Serdaroğlu Vildan, Aydin Ali, Türkmenoğlu Burçin, Usta Asu, Yayli Nurettin
Department of Chemistry, Faculty of Science, Karadeniz Technical University, Trabzon, Turkey.
Department of Basic Medical Science, Faculty of Medicine Bozok University, Yozgat, Turkey.
Turk J Chem. 2023 Feb 28;47(2):476-494. doi: 10.55730/1300-0527.3553. eCollection 2023.
In this study, syntheses of new pyrimidine-coupled -β-glucosides and tetra--acetyl derivatives were carried out. All glycoconjugates were investigated in comparison with known chemotherapeutic agents in terms of their antimicrobial and anticancer functions and DNA/protein binding affinities. Spectral data showed that all glycoside derivatives were obtained by diastereoselectivity as β-anomers. Both tested groups exhibited strong antiproliferative activity (2.29-66.84 μg/mL), but some of them had sufficiently ideal % cytotoxicity values (10.01%-16.78%). And also all synthetic compounds exhibited remarkable antibacterial activity against human pathogenic bacteria. Binding of these compounds to CT-DNA resulted in significant changes in spectral properties, consistent with groove binding. Molecular docking studies of some compounds revealed that the docking score, complex energy, and MM-GBSA ΔG energy values were consistent with the experimental results, which showed that the new compounds were potent chemotherapeutic agents. Overall bioactivity results suggest that these compounds may be candidates as new chemotherapeutic agents and deserve further pharmacological evaluation.
在本研究中，开展了新型嘧啶偶联-β-葡萄糖苷和四乙酰衍生物的合成。所有糖缀合物均与已知化疗药物进行了比较，考察了它们的抗菌、抗癌功能以及DNA/蛋白质结合亲和力。光谱数据表明，所有糖苷衍生物均通过非对映选择性以β-端基异构体形式获得。两个测试组均表现出较强的抗增殖活性（2.29 - 66.84 μg/mL），但其中一些具有足够理想的细胞毒性值（10.01% - 16.78%）。而且所有合成化合物对人类病原菌均表现出显著的抗菌活性。这些化合物与CT-DNA的结合导致光谱性质发生显著变化，这与沟槽结合一致。对一些化合物的分子对接研究表明，对接分数、复合物能量和MM-GBSA ΔG能量值与实验结果一致，表明这些新化合物是有效的化疗药物。总体生物活性结果表明，这些化合物可能作为新型化疗药物的候选物，值得进一步进行药理学评价。
