Abstract

In this work, we evaluated the antiproliferative and anti-inflammatory activities of two diosgenin prodrugs. The prodrugs were obtained by esterification of diosgenin at position 3 with 4-oxo-4-(prop-2-yn-1-yloxy)butanoic acid followed by click reaction on terminal alkyne with 3-azidopropan-1-ol N-alkylated dendrons, resulting in a prodrug with methyl ester end-groups and a derivative with tert-butyl ester end-groups, hydrolysis of tert-butyl ester derivative afforded a prodrug with carboxylic acid terminals. All compounds were fully characterized by ¹H and ¹³C NMR, ATR-FTIR and HR-ESI TOF. Studies of the anti-inflammatory effects on mouse ear edema of prodrugs methyl ester and carboxylic acid, ended, using diosgenin and dexamethasone as positive controls, showed the superiority of methyl ester ended prodrug with an ED₅₀ four times lower than that of dexamethasone. Further, carboxylic acid ended prodrug was found to be more active than diosgenin as an antiproliferative agent, according to crystal violet assay.

Graphic abstract

Diosgenin was transformed to ester and acid prodrugs through succinic ester and a 1,2,3-triazole linkers. The prodrug with methyl ester terminals was four times more active than dexamethasone as anti-inflammatory compound, while prodrug with carboxylic acid terminals improved antiproliferative activity over MCF-7 cells.

中文翻译：

---

薯gen皂素原药的合成：抗炎和抗增殖活性评估

摘要

在这项工作中，我们评估了两种薯os皂苷元前药的抗增殖和抗炎活性。前药是通过在3位将薯os皂苷元与4-氧代-4-（prop-2-yn-1-yloxy）丁酸酯化，然后在末端炔烃上与3-azidopropan-1-ol N-烷基化树枝状分子进行点击反应而获得的。，导致与甲基酯端基的前体药物，并用衍生物叔丁基酯端基，水解叔丁基酯衍生物，得到一个与羧酸端子前药。所有化合物的特征在于¹ H和¹³13 C NMR，ATR-FTIR和HR-ESI TOF。以薯gen皂甙元和地塞米松为阳性对照，对前药甲酯和羧酸对小鼠耳朵水肿的抗炎作用的研究表明，以ED ₅₀为底物的甲基酯终止前药的优越性比地塞米松低四倍。此外，根据结晶紫测定，发现羧酸封端的前药比薯di皂苷元作为抗增殖剂更具活性。

图形摘要

薯gen皂素通过琥珀酸酯和1,2,3-三唑连接基转化为酯和酸的前药。具有甲基末端的前药作为抗炎化合物的活性是地塞米松的四倍，而具有羧酸末端的前药提高了对MCF-7细胞的抗增殖活性。