Mamadalieva Nilufar Z, Hussain Hidayat, Mollica Adriano, Zengin Gokhan, Mamadalieva Rano Z, Elhady Sameh S, Fadil Sana A, Ashour Mohamed L, Youssef Fadia S
Institute of the Chemistry of Plant Substances, Academy Sciences of Uzbekistan, Tashkent 100170, Uzbekistan.
Department of Bioorganic Chemistry, Leibniz Institute of Plant Biochemistry, Weinberg 3, 06120 Halle, Germany.
Life (Basel). 2022 May 31;12(6):824. doi: 10.3390/life12060824.
Ecdysteroids represent arthropods' steroidal hormones, and they exist in about 5-6% of plant species. In this study, the enzyme inhibitory activity of 20 ecdysteroids was assessed for the first time via determining their inhibition versus acetylcholinesterase, butyrylcholinesterase, tyrosinase, as well as α-amylase enzymes. Furthermore, 20-Hydroxyecdysone-2,3,22-tri--acetate () showed the highest inhibition of acetylcholinesterase and butyrylcholinesterase with values of 5.56 and 4.76 mg GALAE/g, respectively. All ecdysteroids displayed tyrosinase inhibitory effects, whereas the most potent was viticosterone E () with 78.88 mg KAE/g. Most ecdysteroids had similar amylase inhibitory properties; meanwhile, the best α-amylase inhibitory potential was observed with viticosterone E-diacetonide () (0.35 mmol ACAE/g). Most of the tested compounds showed tyrosinase inhibitory potential; therefore, they were exposed to molecular docking evaluation using the tyrosinase enzyme. Viticosterone E () showed the best ranking score with a docking score of -5.716 Kcal/mol and made three separate H-bonds with Gly281, Asn81, and His85. From ADMET /TOPKAT in silico evaluation, it was obvious that most of the compounds displayed reasonable pharmacodynamic and pharmacokinetic properties; however, their toxicity should be carefully monitored by adjusting their doses while investigating their activity after incorporation into dosage forms. Principal component analysis (PCA) based upon the in vitro and in silico data was carried out to visualize the differences between the tested compounds better. PCA score plot successfully classifies the compounds into four main clusters that, in turn, reflects the similarities and differences among the clustered compounds with respect to their biological, pharmacokinetic, and pharmacodynamic properties that are mainly influenced by the similarity in the chemical structure. Thus, ecdysteroids can act as effective drug entities for alleviating several disorders owing to their enzyme inhibitory potential.
蜕皮甾类是节肢动物的甾体激素，存在于约5% - 6%的植物物种中。在本研究中，首次通过测定20种蜕皮甾类对乙酰胆碱酯酶、丁酰胆碱酯酶、酪氨酸酶以及α -淀粉酶的抑制作用，评估了它们的酶抑制活性。此外，20 -羟基蜕皮酮 - 2,3,22 - 三 - 乙酸酯（）对乙酰胆碱酯酶和丁酰胆碱酯酶的抑制作用最强，其值分别为5.56和4.76 mg GALAE/g。所有蜕皮甾类均表现出酪氨酸酶抑制作用，其中最有效的是葡萄甾酮E（），为78.88 mg KAE/g。大多数蜕皮甾类具有相似的淀粉酶抑制特性；同时，葡萄甾酮E - 双丙酮化物（）对α -淀粉酶的抑制潜力最佳（0.35 mmol ACAE/g）。大多数受试化合物表现出酪氨酸酶抑制潜力；因此，使用酪氨酸酶对它们进行了分子对接评估。葡萄甾酮E（）的对接得分最佳，为 - 5.716 Kcal/mol，并与Gly281、Asn81和His85形成了三个独立的氢键。从ADMET / TOPKAT的计算机模拟评估中可以明显看出，大多数化合物表现出合理的药效学和药代动力学特性；然而，在将它们制成剂型研究其活性时，应通过调整剂量仔细监测其毒性。基于体外和计算机模拟数据进行了主成分分析（PCA），以更好地可视化受试化合物之间的差异。PCA得分图成功地将化合物分为四个主要簇，这反过来反映了聚类化合物在其主要受化学结构相似性影响的生物学、药代动力学和药效学特性方面的异同。因此，蜕皮甾类因其酶抑制潜力可作为缓解多种疾病的有效药物实体。
