Das Abhi, Dutta Sanjay
Organic and Medicinal Chemistry Division, CSIR-Indian Institute of Chemical Biology, Kolkata 700 032, India.
ACS Omega. 2021 Jul 9;6(28):18344-18351. doi: 10.1021/acsomega.1c02207. eCollection 2021 Jul 20.
G-quadruplex, a unique DNA quartet motif with a pivotal role in regulation of the gene expression, has been established as a potent therapeutic target for the treatment of cancer. Small-molecule-mediated stabilization of the G-quadruplex and thus inhibition of the expression from the oncogene promoter and telomere region may be a promising anticancer strategy. -derived natural compounds like aloe emodin, aloe emodin-8-glucoside, and aloin have significant anticancer activity. Comparative binding studies of these three molecules with varieties of G-quadruplex sequences were carried out using different biophysical techniques like absorption spectral titration, fluorescence spectral titration, dye displacement, ferrocyanide quenching assay, and CD and DSC thermogram studies. Overall, this study revealed aloe emodin and aloe emodin-8-glucoside as potent quadruplex-binding molecules mostly in the case of and sequences with a binding affinity value of 10 order that is higher than their duplex DNA binding ability. This observation may be correlated to the anticancer activity of these aloe-active compounds and also be helpful in the potential therapeutic application of natural compound-based molecules.
G-四链体是一种独特的DNA四重基序，在基因表达调控中起关键作用，已被确立为癌症治疗的有效靶点。小分子介导的G-四链体稳定化，进而抑制癌基因启动子和端粒区域的表达，可能是一种有前景的抗癌策略。芦荟大黄素、芦荟大黄素-8-葡萄糖苷和芦荟素等源自芦荟的天然化合物具有显著的抗癌活性。使用吸收光谱滴定、荧光光谱滴定、染料置换、亚铁氰化物猝灭测定以及圆二色光谱（CD）和差示扫描量热法（DSC）热谱研究等不同生物物理技术，对这三种分子与各种G-四链体序列进行了比较结合研究。总体而言，这项研究表明芦荟大黄素和芦荟大黄素-8-葡萄糖苷是有效的四链体结合分子，在大多数情况下，对于特定序列，其结合亲和力值比其与双链DNA的结合能力高10个数量级。这一观察结果可能与这些芦荟活性化合物的抗癌活性相关，也有助于基于天然化合物的分子的潜在治疗应用。
