Department of Pharmaceutics, College of Pharmacy, King Khalid University, Abha 62529, Saudi Arabia.
Department of Medicinal Chemistry, Faculty of Pharmacy, Minia University, Minia 61519, Egypt.
Molecules. 2022 Dec 28;28(1):262. doi: 10.3390/molecules28010262.
Curcumin is a natural polyphenolic compound with well-known anticancer properties. Poor solubility and permeability hamper its use as an anticancer pharmaceutical product. In this study, L-arginine, a basic amino acid and a small hydrophilic molecule, was utilized to form a salt with the weak acid curcumin to enhance its solubility and potentiate the anticancer activities of curcumin. Two methods were adopted for the preparation of curcumin: L-arginine salt, namely, physical mixing and coprecipitation. The ion pair or salt was characterized for docking, solubility, DSC, FTIR, XRD, in vitro dissolution, and anticancer activities using MCF7 cell lines. The molecular docking suggested a salt/ion-pair complex between curcumin and L-arginine. Curcumin solubility was increased 335- and 440-fold by curcumin in L-arginine, physical, and co-precipitated mixtures, respectively. Thermal and spectral analyses supported the molecular docking and formation of a salt/ion pair between curcumin and L-arginine. The cytotoxicity of curcumin L-arginine salt significantly improved (p < 0.05) by 1.4-fold, as evidenced by the calculated IC50%, which was comparable to Taxol (the standard anticancer drug but with common side effects).
姜黄素是一种具有良好抗癌特性的天然多酚化合物。较差的溶解性和通透性阻碍了其作为抗癌药物的应用。在这项研究中，精氨酸，一种碱性氨基酸和小的亲水性分子，被用来与弱酸性姜黄素形成盐，以提高其溶解性并增强姜黄素的抗癌活性。采用两种方法制备姜黄素：精氨酸盐，即物理混合和共沉淀。采用对接、溶解度、DSC、FTIR、XRD、体外溶解和 MCF7 细胞系抗癌活性对离子对或盐进行了表征。分子对接表明姜黄素和精氨酸之间形成了盐/离子对复合物。姜黄素在精氨酸、物理混合物和共沉淀混合物中的溶解度分别提高了 335 倍和 440 倍。热分析和光谱分析支持了分子对接以及姜黄素和精氨酸之间盐/离子对的形成。姜黄素精氨酸盐的细胞毒性显著提高（p<0.05），IC50%的计算值提高了 1.4 倍，与紫杉醇（标准抗癌药物，但有常见副作用）相当。
