Mohandoss Sonaimuthu, Atchudan Raji, Immanuel Edison Thomas Nesakumar Jebakumar, Mandal Tapas Kumar, Palanisamy Subramanian, You SangGuan, Napoleon Ayyakannu Arumugam, Shim Jae-Jin, Lee Yong Rok
School of Chemical Engineering, Yeungnam University, Gyeongsan, Gyeongbuk-do 38541, Republic of Korea.
Department of Marine Food Science and Technology, Gangneung-Wonju National University, 120 Gangneungdaehangno, Gangneung, Gangwon 25457, Republic of Korea.
Carbohydr Polym. 2019 Nov 15;224:115166. doi: 10.1016/j.carbpol.2019.115166. Epub 2019 Aug 5.
This study improves the water solubility and cellular uptake of guanosine (GuN) through an inclusion complexation with cyclodextrin derivatives (CDs), namely β-cyclodextrin (β-CD), hydroxypropyl-β-cyclodextrin (HP-β-CD), and sulfobutyl ether-β-cyclodextrin (SBE-β-CD). Inclusion complexes of GuN and CDs are synthesized in a 1:1 stoichiometric ratio with binding constants calculated using the Benesi-Hildebrand method. Characterizations of the prepared solid complexes using FTIR, XRD, TGA-DSC, and SEM indicate that GuN is found inside the cavity of the CDs. Moreover, in silico molecular modeling analysis identifies the most favorable binding interactions of GuN deeply encapsulated in the hydrophobic cavities of the CDs, as validated by PatchDock and FireDock servers. In addition, human breast cancer MCF-7 cell activity indicates that the SBE-β-CD:GuN complex displays better cell viability and cellular uptake than GuN or other inclusion complexes of β-CD:GuN and HP-β-CD:GuN.
本研究通过与环糊精衍生物（CDs），即β-环糊精（β-CD）、羟丙基-β-环糊精（HP-β-CD）和磺丁基醚-β-环糊精（SBE-β-CD）形成包合物，提高了鸟苷（GuN）的水溶性和细胞摄取。GuN与CDs的包合物以1:1化学计量比合成，并使用贝内西-希尔德布兰德方法计算结合常数。使用傅里叶变换红外光谱（FTIR）、X射线衍射（XRD）、热重-差示扫描量热法（TGA-DSC）和扫描电子显微镜（SEM）对制备的固体复合物进行表征，结果表明GuN存在于CDs的腔内。此外，计算机模拟分子建模分析确定了GuN在CDs疏水腔内的最有利结合相互作用，这已通过PatchDock和FireDock服务器得到验证。此外，人乳腺癌MCF-7细胞活性表明，SBE-β-CD:GuN复合物比GuN或β-CD:GuN和HP-β-CD:GuN的其他包合物表现出更好的细胞活力和细胞摄取。
