Department of Chemistry, Federal University of Mato Grosso, Cuiabá-MT, 78060-900, Brazil.
Engineering Faculty, Federal University of Mato Grosso, Várzea Grande-MT, 78060-900, Brazil.
Chem Biodivers. 2022 Dec;19(12):e202200586. doi: 10.1002/cbdv.202200586. Epub 2022 Dec 13.
In the current work, we describe the synthesis of 1,4-dihydropyridine (1,4-DHP) derivatives via Hantzsch multicomponent reaction and their evaluation as photosystem II (PSII) inhibitors through chlorophyll a fluorescence bioassay. Among all the compounds tested, 1,1'-(2,4,6-trimethyl-1,4-dihydropyridine-3,5-diyl)bis(ethan-1-one) (4b) showed best results, reducing the parameters performance index on absorption basis (PI ) and electron transport per reaction center by 61 % and 49 %, respectively, as compared to the control. These results indicate the inhibitory activity of PSII over the electron transport chain. Additionally, a molecular docking approach using the protein D1 (PDB code 4V82) was performed in order to assess the structure-activity relationship among the 1,4-DHP derivatives over the PSII, which revealed that both, size of the group at position 4 and the carbonyl groups at the dihydropyridine ring are important for the ligand's interaction, particularly for the hydrogen-bonding interaction with the residues His215, Ser264, and Phe265. Thus, the optimization of these molecular features is the aim of our research group to extend the knowledge of PSII electron chain inhibitors and the establishment of new potent bioactive molecular scaffolds.
在当前的工作中，我们描述了通过 Hantzsch 多组分反应合成 1,4-二氢吡啶（1,4-DHP）衍生物，并通过叶绿素 a 荧光生物测定法评估它们作为光系统 II（PSII）抑制剂的效果。在所测试的所有化合物中，1,1'-(2,4,6-三甲基-1,4-二氢吡啶-3,5-二基)双(乙-1-酮)（4b）表现出最好的结果，与对照相比，吸收基础上的参数性能指数（PI）和每反应中心的电子传递分别降低了 61%和 49%。这些结果表明 PSII 对电子传递链具有抑制活性。此外，还使用蛋白 D1（PDB 代码 4V82）进行了分子对接方法，以评估 1,4-DHP 衍生物在 PSII 上的结构-活性关系，结果表明，在位置 4 的基团大小和二氢吡啶环上的羰基对于配体的相互作用都是重要的，特别是与残基 His215、Ser264 和 Phe265 的氢键相互作用。因此，优化这些分子特征是我们研究小组的目标，旨在扩展 PSII 电子链抑制剂的知识，并建立新的有效的生物活性分子支架。
