Laboratório de Imunopatologia Keizo Asami (LIKA), Universidade Federal de Pernambuco, 50670-901, Brazil.
Universidade da Integração Internacional da Lusofonia Afro-Brasileira (UNILAB), 62790-970 Redenção, CE, Brazil.
Int J Biol Macromol. 2021 Feb 15;170:622-635. doi: 10.1016/j.ijbiomac.2020.12.153. Epub 2021 Jan 5.
In this study, we report the synthesis of eight novel indole-thiazole and indole-thiazolidinone derivatives, as well as their ability to interact with DNA, analysed through the UV-vis absorption, fluorescence, circular dichroism (CD), viscosity techniques and molecular docking. The ctDNA interaction analysis demonstrated different spectroscopic effects and the affinity constants (Kb) calculated by the UV-vis absorption method were between 2.08 × 10 and 6.99 × 10 M, whereas in the fluorescence suppression constants (Ksv) ranged between 0.38 and 0.77 × 10 M and 0.60-7.59 × 10 M using Ethidium Bromide (EB) and 4',6-Diamidino-2-phenylindole (DAPI) as fluorescent probes, respectively. Most derivatives did not alter significantly the secondary structure of the ctDNA according to the CD results. None of the compounds was able to change the relative viscosity of the ctDNA. These results prove that compounds interact with ctDNA via groove binding, which was confirmed by A-T rich oligonucleotide sequence assay with compound JF-252, suggesting the importance of both the phenyl ring coupled to C-4 thiazole ring and the bromo-unsubstituted indole nucleus.
在这项研究中，我们报告了八种新型吲哚噻唑和吲哚噻唑烷酮衍生物的合成，以及它们通过紫外可见吸收、荧光、圆二色性（CD）、粘度技术和分子对接分析与 DNA 相互作用的能力。ctDNA 相互作用分析显示了不同的光谱效应，通过紫外可见吸收法计算的亲和常数（Kb）在 2.08×10 和 6.99×10 M 之间，而在荧光抑制常数（Ksv）中，使用溴化乙锭（EB）和 4'，6-二脒基-2-苯基吲哚（DAPI）作为荧光探针，范围分别在 0.38 和 0.77×10 M 和 0.60-7.59×10 M 之间。大多数衍生物根据 CD 结果并没有显著改变 ctDNA 的二级结构。没有一种化合物能够改变 ctDNA 的相对粘度。这些结果证明化合物通过沟结合与 ctDNA 相互作用，这在与化合物 JF-252 的富含 A-T 的寡核苷酸序列测定中得到了证实，这表明与 C-4 噻唑环相连的苯基环和未取代的溴吲哚核都很重要。
