Korkmaz Adem, Kurtay Gülbin, Kaya Esin, Bursal Ercan
Faculty of Health Sciences, Muş Alparslan University, Muş, Turkey.
Department of Chemistry, Faculty of Science, Ankara University, Ankara, Turkey.
J Biomol Struct Dyn. 2023 Sep-Oct;41(15):7128-7143. doi: 10.1080/07391102.2022.2116600. Epub 2022 Sep 7.
One of the primary purposes of this study is to synthesize new aryl sulfonate-naphthalene hybrid structures possessing divergent electron-withdrawing and electron-releasing functional groups. Following the improved reaction conditions, we successfully gathered ten distinct sulfonate derivatives () with good yields. The synthesized naphthalene-based sulfonate derivatives were then characterized using appropriate analytical methods (FT-IR, H-NMR, C-NMR, HRMS, and elemental analysis). Additionally, and enzyme inhibitory properties of the prepared aryl sulfonate-naphthalene hybrid structures were evaluated against pancreatic lipase and tyrosinase enzymes. Corresponding enzyme activity investigations revealed that the produced compounds inhibit pancreatic lipase and tyrosinase enzymes significantly. According to the lowest IC values, (95.3 ± 4.0 µM) demonstrated the most effective inhibition against pancreatic lipase, whereas (40.8 ± 3.3 µM) was found as the most effective inhibition against the tyrosinase. According to studies, exhibited the highest affinity value (-9.9 kcal/mol) against pancreatic lipase, whereas demonstrated the best affinity value (-8.7 kcal/mol) against tyrosinase.Furthermore, we investigated various structural and physicochemical properties of the target molecules, namely frontier orbital' (HOMO, LUMO, and bandgap) energies (including their corresponding contour plots), global reactivity descriptors (ionization energy and electron affinity), and electronegativity values gathered from ground-state (GS) density functional theory (DFT) calculations. These investigations demonstrated that the observed electrostatic interactions effectively contributed to the studied molecules' experimentally demonstrated enzyme inhibition potential. Also, ADMET studies were evaluated to enlighten the molecular interactions of the compounds with the enzymes.Communicated by Ramaswamy H. Sarma.
本研究的主要目的之一是合成具有不同吸电子和供电子官能团的新型芳基磺酸盐 - 萘杂化结构。遵循改进的反应条件，我们成功地以良好的产率获得了十种不同的磺酸盐衍生物（）。然后使用适当的分析方法（傅里叶变换红外光谱、氢核磁共振、碳核磁共振、高分辨质谱和元素分析）对合成的基于萘的磺酸盐衍生物进行了表征。此外，还评估了所制备的芳基磺酸盐 - 萘杂化结构对胰腺脂肪酶和酪氨酸酶的酶抑制特性。相应的酶活性研究表明，所产生的化合物对胰腺脂肪酶和酪氨酸酶有显著抑制作用。根据最低的半数抑制浓度值，（95.3±4.0μM）对胰腺脂肪酶表现出最有效的抑制作用，而（40.8±3.3μM）被发现是对酪氨酸酶最有效的抑制作用。根据研究，对胰腺脂肪酶表现出最高的亲和力值（-9.9 kcal/mol），而对酪氨酸酶表现出最佳的亲和力值（-8.7 kcal/mol）。此外，我们研究了目标分子的各种结构和物理化学性质，即前线轨道（最高占据分子轨道、最低未占据分子轨道和带隙）能量（包括其相应的等高线图）、全局反应性描述符（电离能和电子亲和能）以及从基态密度泛函理论计算得出的电负性值。这些研究表明，观察到的静电相互作用有效地促成了所研究分子实验证明的酶抑制潜力。此外，还进行了药物代谢及毒性研究以阐明化合物与酶的分子相互作用。由拉马斯瓦米·H·萨尔马传达。
