Institute of Chemistry, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan.
H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
Biomed Res Int. 2022 Jul 6;2022:6865472. doi: 10.1155/2022/6865472. eCollection 2022.
Betamethasone is an important glucocorticoids (GCs), frequently used to cure allergies (such as asthma and angioedema), Crohn's disease, skin diseases (such as dermatitis and psoriasis), systemic lupus erythematosus, rheumatic disorders, and leukemia. Present investigation deals to find potential agonist of glucocorticoid receptors after biotransformation of betamethasone dipropionate (1) and to carry out the molecular docking and ADME analyses. Biotransformation of 1 was carried out with (dandy) roots and (banana) leaves. furnished low-cost value-added products such as Sananone dipropionate (2) in 5% yields. Further, biocatalysis of Sananone dipropionate (2) with gave Sananone propionate (3) and Sananone (4) in 12% and 7% yields, respectively. However, Sananone (4) was obtained in 37% yields from . Compound 5 was obtained in 11% yield after -elimination of propionic acid at C-17 during oxidation of compound 1. The structure elucidation of new compounds 2-5 was accomplished through combined use of X-ray diffraction and NMR (1D and 2D) studies. In addition to this, molecular docking and ADME analyses of all transformed products of 1 were also done. Compounds 1-5 showed -12.53 to -10.11 kcal/mol potential binding affinity with glucocorticoid receptor (GR) and good ADME profile. Moreover, all the compounds showed good oral bioavailability with the octanol/water partition coefficient in the range of 2.23 to 3.65, which indicated that compounds 1-5 were in significant agreement with the given criteria to be considered as drug-like.
倍他米松是一种重要的糖皮质激素（GCs），常用于治疗过敏（如哮喘和血管性水肿）、克罗恩病、皮肤病（如皮炎和银屑病）、系统性红斑狼疮、风湿性疾病和白血病。本研究旨在寻找倍他米松二丙酸酯（1）生物转化后的潜在糖皮质激素受体激动剂，并进行分子对接和 ADME 分析。用（黄莲）根和（芭蕉）叶对 1 进行了生物转化。（黄莲）根和（芭蕉）叶提供了低成本的增值产品，如萨那酮二丙酸酯（2），产率为 5%。此外，用（香蕉）叶生物催化萨那酮二丙酸酯（2）得到萨那酮丙酸酯（3）和萨那酮（4），产率分别为 12%和 7%。然而，从（黄莲）根中得到萨那酮（4）的产率为 37%。在化合物 1 的氧化过程中，通过在 C-17 位消除丙酸，得到化合物 5，产率为 11%。新化合物 2-5 的结构通过 X 射线衍射和 NMR（1D 和 2D）研究的综合使用得到阐明。除此之外，还对 1 的所有转化产物进行了分子对接和 ADME 分析。化合物 1-5 与糖皮质激素受体（GR）的潜在结合亲和力为-12.53 至-10.11 kcal/mol，具有良好的 ADME 特征。此外，所有化合物的辛醇/水分配系数均在 2.23 至 3.65 之间，具有良好的口服生物利用度，这表明化合物 1-5 与给定标准非常一致，可被认为是类药性的。
