Department of Chemistry, Allama Iqbal Open University, 44000 Islamabad, Pakistan.
Department of Chemistry, Allama Iqbal Open University, 44000 Islamabad, Pakistan.
Int J Biol Macromol. 2024 Apr;263(Pt 1):130231. doi: 10.1016/j.ijbiomac.2024.130231. Epub 2024 Feb 17.
Three newly synthesized amantadine thiourea conjugates namely MS-1 N-(((3 s,5 s,7 s)-adamantan-1-yl)carbamothioyl)benzamide, MS-2 N-(((3 s,5 s,7 s)-adamantan-1-yl)carbamothioyl)-4-methylbenzamide and MS-3 N-((3 s,5 s,7 s)-adamantan-1-ylcarbamothioyl)-4-chlorobenzamide were investigated for their structures, bindings (DNA/ elastase), and for their impact on healthy and cancerous cells. Theoretical (DFT/docking) and experimental {UV-visible (UV-), fluorescence (Flu-), and cyclic voltammetry (CV)} studies indicated binding interactions of each conjugate with DNA and elastase enzyme. Theoretically and experimentally calculated binding parameters for conjugate - DNA interaction revealed MS-3 - DNA to have most significant binding with comparatively greater values of binding parameters {(K/M: docking, 3.8 × 10; UV-, 5.95 × 10; Flu-,1.55 × 10; CV, 1.52 × 10), (∆G/ kJmol: docking, -32.09; UV-, -22.40; Flu-,-30.81; CV, -24.82)}. The docked structures, greater bindings site size values (n), and the trend in DNA viscosity changes in the presence of each conjugate concentration confirmed a mixed binding mode of interaction among them. Conjugate - elastase binding by docking agreed with the experimental anti-elastase findings. Cytotoxicity studies of each tested conjugate demonstrated greater cytotoxicity for cancerous (MG-U87) cells in comparison to control, while for the normal (HEK-293) cells the cytotoxicity was found comparatively low. Overall exploration suggested that MS-3 is the most effective candidate for DNA binding, anti-elastase, and for anti-glioma activities.
三种新合成的金刚烷硫脲缀合物，即 MS-1 N-(((3s,5s,7s)-金刚烷-1-基)氨甲酰硫基)苯甲酰胺、MS-2 N-(((3s,5s,7s)-金刚烷-1-基)氨甲酰硫基)-4-甲基苯甲酰胺和 MS-3 N-((3s,5s,7s)-金刚烷-1-基氨甲酰硫基)-4-氯苯甲酰胺，对其结构、结合物（DNA/弹性蛋白酶）以及对健康细胞和癌细胞的影响进行了研究。理论（DFT/对接）和实验{紫外可见（UV-）、荧光（Flu-）和循环伏安法（CV）}研究表明，每个缀合物与 DNA 和弹性蛋白酶酶的结合相互作用。理论和实验计算的结合参数表明，与 DNA 相互作用的 MS-3-DNA 具有最显著的结合，具有比较大的结合参数值{(K/M：对接，3.8×10；UV-，5.95×10；Flu-，1.55×10；CV，1.52×10)，(∆G/kJmol：对接，-32.09；UV-，-22.40；Flu-，-30.81；CV，-24.82)}。对接结构、较大的结合部位大小值（n）以及存在每个缀合物浓度时 DNA 粘度变化的趋势证实了它们之间的混合结合模式。对接的缀合物-弹性蛋白酶结合与实验抗弹性蛋白酶结果一致。每个测试缀合物的细胞毒性研究表明，与对照相比，对癌细胞（MG-U87）的细胞毒性更大，而对正常（HEK-293）细胞的细胞毒性则较低。总的探索表明，MS-3 是结合 DNA、抗弹性蛋白酶和抗神经胶质瘤活性的最有效候选物。
