Solasodine analogues containing a seven-membered F ring with a nitrogen atom placed at position 22a were prepared from diosgenin or tigogenin in a four-step synthesis comprising of the simultaneous opening of the F-ring and introduction of cyanide in position 22α, activation of the 26-hydroxyl group as mesylate, nitrile reduction, and N-cyclization. Solasodine, six obtained 22a(N)-homo analogues, as well as four 26a-homosolasodine derivatives and their open-chain precursors (13 in total) were tested as potential inhibitors of acetyl- and butyryl-cholinesterases and showed activity at micromolar concentrations. The structure-activity relationship study revealed that activities against studied esterases are affected by the structure of E/F rings and the substitution pattern of ring A. The most potent compound 8 acted as non-competitive inhibitors and exerted IC₅₀ = 8.51 μM and 7.05 μM for eeAChE and eqBChE, respectively. Molecular docking studies revealed the hydrogen bond interaction of 8 with S293 of AChE; further rings are stabilized via hydrophobic interaction (ring A) or interaction with Y341 and W286 (rings B and C). Biological experiments showed no neurotoxicity of differentiated SH-SY5Y cells. More importantly, results from neuroprotective assay based on glutamate-induced cytotoxicity revealed that most derivatives had the ability to increase the viability of differentiated SH-SY5Y cells in comparison to galantamine and lipoic acid assayed as standards. The newly synthesized solasodine analogues are able to inhibit and to bind cholinesterases in noncompetitive mode of inhibition and exhibited neuroprotection potential of differentiated neuroblastoma cells after Glu-induced toxicity.

由薯os皂苷元或tigogenin进行四步合成，其中包括同时打开F环并在22α位引入氰化物，活化硅藻土素，其中含有七元F环且氮原子位于22a位的Solaso​​dine类似物26-羟基为甲磺酸酯，腈还原和N-环化。Solaso​​dine，六种获得22a（N-homo类似物，以及四个26a-homosolaso​​dine衍生物及其开链前体（共13个）经测试可作为乙酰基和丁酰胆碱酯酶的潜在抑制剂，并在微摩尔浓度下显示活性。结构-活性关系研究表明，针对所研究酯酶的活性受E / F环的结构和A环的取代模式的影响。最有效的化合物8充当非竞争性抑制剂，发挥的IC ₅₀ = 8.51μM和7.05 eeAChE和eqBChE分别为μM。分子对接研究揭示了8与AChE的S293的氢键相互作用。通过进一步稳定环疏水相互作用（环A）或与Y341和W286的相互作用（环B和C）。生物学实验未显示分化的SH-SY5Y细胞的神经毒性。更重要的是，基于谷氨酸诱导的细胞毒性的神经保护试验结果表明，与标准的加兰他敏和硫辛酸相比，大多数衍生物具有增加分化的SH-SY5Y细胞活力的能力。新合成的索拉索定类似物能够以非竞争性抑制方式抑制并结合胆碱酯酶，并在Glu诱导的毒性作用下展现出分化的神经母细胞瘤细胞的神经保护潜力。