Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11221 Belgrade, Serbia.
Molecules. 2011 Mar 23;16(3):2658-71. doi: 10.3390/molecules16032658.
In this study the solvolysis of newly synthesized fluocinolone acetonide C-21 esters was analysed in comparison with fluocinonide during a 24-hour period of time. The solvolysis was performed in an ethanol-water (90:10 v/v) mixture using the excess of NaHCO₃. The solvolytic mixtures of each investigated ester have been assayed by a RP-HPLC method using isocratic elution with methanol-water (75:25 v/v); flow rate 1 mL/min; detection at 238 nm; temperature 25 °C. Solvolytic rate constants were calculated from the obtained data. Geometry optimizations and charges calculations were carried out by Gaussian W03 software. A good correlation (R = 0.9924) was obtained between solvolytic rate constants and the polarity of the C-O2 bond of those esters. The established relation between solvolytic rate constant (K) and lipophilicity (cLogP) with experimental anti-inflammatory activity could be indicative for topical corticosteroid prodrug activation.
在这项研究中，对新合成的氟轻松丙酮缩酮 C-21 酯的溶剂解作用进行了分析，并与氟轻松进行了比较，研究时间为 24 小时。溶剂解在乙醇-水（90:10v/v）混合物中使用过量的 NaHCO₃进行。通过反相高效液相色谱法（RP-HPLC），以甲醇-水（75:25v/v）为等度洗脱剂，以 1 mL/min 的流速、238nm 的检测波长、25°C 的温度，对每种被研究的酯的溶剂解混合物进行了检测。从获得的数据中计算出溶剂解速率常数。采用 Gaussian W03 软件进行几何优化和电荷计算。溶剂解速率常数与酯的 C-O2 键极性之间存在良好的相关性（R = 0.9924）。建立的溶剂解速率常数（K）与亲脂性（cLogP）与实验抗炎活性之间的关系可能表明局部皮质类固醇前药的激活。
