Khodair Ahmed I, Alzahrani Fatimah M, Awad Mohamed K, Al-Issa Siham A, Al-Hazmi Ghaferah H, Nafie Mohamed S
Chemistry Department, Faculty of Science, Kafrelsheikh University, 33516 Kafrelsheikh, Egypt.
Department of Chemistry, College of Science, Princess Nourah bint Abdulrahman University, Riyadh 11671, Saudi Arabia.
ACS Omega. 2023 Mar 28;8(14):13300-13314. doi: 10.1021/acsomega.3c00641. eCollection 2023 Apr 11.
Nitrogen and sulfur glycosylation was carried out via the reaction of rhodanine () with α-acetobromoglucose under basic conditions. Deacetylation of the protected nitrogen nucleoside was performed with CHONa in CHOH without cleavage of the rhodanine ring to afford the deprotected nitrogen nucleoside . Further, deacetylation of the protected sulfur nucleoside was performed with CHONa in CHOH with the cleavage of the rhodanine ring to give the hydrolysis product . The protected nitrogen nucleosides - were produced by condensing the protected nitrogen nucleoside with the aromatic aldehydes - in CHOH while using morpholine as a secondary amine catalyst. Deacetylation of the protected nitrogen nucleosides - was performed with NaOCH/CHOH without cleavage of the rhodanine ring to afford the deprotected nitrogen nucleosides -. NMR spectroscopy was used to designate the anomers' configurations. To examine the electrical and geometric properties derived from the stable structure of the examined compounds, molecular modeling and DFT calculations using the B3LYP/6-31+G (d,p) level were carried out. The quantum chemical descriptors and experimental findings showed a strong connection. The IC values for most compounds were very encouraging when evaluated against MCF-7, HepG2, and A549 cancer cells. Interestingly, IC values for , , and were much lower than those for Doxorubicin (7.67, 8.28, 6.62 μM): (3.7, 8.2, 9.8 μM), (3.1, 13.7, 21.8 μM), and (7.17, 2.2, 4.5 μM), respectively. Against Topo II inhibition and DNA intercalation, when compared to Dox (IC = 9.65 and 31.27 μM), compound showed IC values of 7.3 and 18.2 μM, respectively. In addition, compound induced a 65.6-fold increase in the rate of apoptotic cell death in HepG2 cells, with the cell cycle being arrested in the G2/M phase as a result. Additionally, it upregulated the apoptosis-mediated genes of P53, Bax, and caspase-3,8,9 by 9.53, 8.9, 4.16, 1.13, and 8.4-fold change, while it downregulated the Bcl-2 expression by 0.13-fold. Therefore, glucosylated Rhodanines may be useful as potential therapeutic candidates against cancer because of their topoisomerase II and DNA intercalation activity.
氮和硫糖基化反应是通过若丹宁（）与α - 乙酰溴葡萄糖在碱性条件下反应进行的。用甲醇钠在甲醇中对受保护的氮核苷进行脱乙酰化反应，且不裂解若丹宁环，得到脱保护的氮核苷。此外，用甲醇钠在甲醇中对受保护的硫核苷进行脱乙酰化反应时，若丹宁环会裂解，得到水解产物。受保护的氮核苷 - 是通过在甲醇中，以吗啉作为仲胺催化剂，使受保护的氮核苷与芳香醛 - 缩合制得的。用甲醇钠/甲醇对受保护的氮核苷 - 进行脱乙酰化反应，且不裂解若丹宁环，得到脱保护的氮核苷 - 。利用核磁共振光谱确定端基异构体的构型。为了研究所检测化合物稳定结构衍生出的电学和几何性质，使用B3LYP/6 - 31 + G(d,p)水平进行了分子建模和密度泛函理论计算。量子化学描述符与实验结果显示出紧密联系。当针对MCF - 7、HepG2和A549癌细胞进行评估时，大多数化合物的半数抑制浓度（IC）值非常令人鼓舞。有趣的是，，和的IC值远低于阿霉素的IC值（7.67、8.28、6.62 μM）：分别为（3.7、8.2、9.8 μM），（3.1、13.7、21.8 μM）和（7.17、2.2、4.5 μM）。与阿霉素（IC = 9.65和31.27 μM）相比，在拓扑异构酶II抑制和DNA嵌入方面，化合物的IC值分别为7.3和18.2 μM。此外，化合物在HepG2细胞中诱导凋亡细胞死亡率增加了65.6倍，结果细胞周期停滞在G2/M期。此外，它使凋亡介导基因P53、Bax和半胱天冬酶 - 3、8、9上调了9.53、8.9、4.16、1.13和8.4倍，同时使Bcl - 2表达下调了0.13倍。因此，糖基化若丹宁因其拓扑异构酶II和DNA嵌入活性，可能作为潜在的抗癌治疗候选物。
