Suwandecha Tan, Rungnim Chompoonut, Namuangruk Supawadee, Ruktanonchai Uracha, Sawatdee Somchai, Dechraksa Janwit, Srichana Teerapol
NANOTEC PSU Center of Excellence on Drug Delivery and Department of Pharmacology, Faculty of Sciences, Prince of Songkla University, Hat Yai, Songkhla 90112, Thailand.
NANOTEC, National Science and Technology Development Agency (NSTDA), 111 Thailand Science Park, Thanon Phahonyothin, Tambon Khlong Nueng, Amphoe Khlong Luang, Pathum Thani 12120, Thailand.
J Mol Graph Model. 2017 Oct;77:115-120. doi: 10.1016/j.jmgm.2017.08.011. Epub 2017 Aug 18.
Sildenafil (SF) was included in cyclodextrins (CD) to enhance its solubility. Spectrofluorometry was used to confirm the complexation constant (stability constant). The orientations of SF inside the β-CDs and γ-CDs were fully illustrated. Molecular dynamics simulations were performed on two inclusion complexes (β-CD/SF and γ-CD/SF) in the aqueous system. The polar methylpiperazine group was found to locate inside the β-CD cavity, both in the wide and narrow side and was positioned 2°A from the center. In contrast, the methylpiperazine group did not fit well within the γ-CD cavity. Moreover, these results also confirmed hydrogen bonding that the highest number of bonding formed between the polar methylpiperazine sulfonyl structure and the hydroxyl group of β-CD. The simulated binding free energy of the methylpiperazine-β-CD inclusion complex (-6.01kcal/mol), featured a large contribution from electrostatic and van der Waals forces, which was the most stable complex. The association constant of β-CD/SF (12.3) was higher than γ-CD/SF (3.3) and confirmed with in silico measurements of binding free energy. In summary, SF forms a stable complex with β-CD.
西地那非（SF）被包合于环糊精（CD）中以提高其溶解度。采用荧光光谱法确定络合常数（稳定常数）。全面阐述了SF在β-环糊精和γ-环糊精内部的取向。在水体系中对两种包合物（β-环糊精/SF和γ-环糊精/SF）进行了分子动力学模拟。发现极性甲基哌嗪基团位于β-环糊精空腔内，在宽边和窄边均有，且距离中心2埃。相比之下，甲基哌嗪基团在γ-环糊精空腔内不太合适。此外，这些结果还证实了氢键的存在，即极性甲基哌嗪磺酰基结构与β-环糊精的羟基之间形成的氢键数量最多。甲基哌嗪-β-环糊精包合物的模拟结合自由能为-6.01千卡/摩尔，静电和范德华力贡献较大，是最稳定的络合物。β-环糊精/SF的缔合常数（12.3）高于γ-环糊精/SF（3.3），并通过结合自由能的计算机模拟测量得到证实。总之，SF与β-环糊精形成稳定的络合物。
