Key Laboratory of Marine Drugs, The Ministry of Education of China, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, People's Republic of China; Laboratory for Marine Drugs and Bioproducts, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266200, People's Republic of China; State Key Laboratory for Marine Corrosion and Protection, Luoyang Ship Material Research Institute (LSMRI), Qingdao 266061, People's Republic of China.
Key Laboratory of Marine Drugs, The Ministry of Education of China, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, People's Republic of China; Laboratory for Marine Drugs and Bioproducts, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266200, People's Republic of China.
Eur J Med Chem. 2018 Feb 25;146:232-244. doi: 10.1016/j.ejmech.2018.01.057. Epub 2018 Feb 4.
Terphenyllin (1), a naturally abundant p-terphenyl metabolite, was isolated from the coral derived fungus Aspergillus candidus together with four natural analogues 2-5. To evaluate their potency and selectivity, a series of new derivatives of 1 were designed and semisynthesized. They were evaluated for their α-glucosidase inhibitory, cytotoxic, and antibacterial activities. Compounds 1, 3, 4, 7, 8, 10, 11, 14, 15, 21, 23, 24, 29, 39, and 40 showed significant α-glucosidase inhibitory activity with IC values of 4.79-15 μM, which were stronger than that of the positive controls, 1-deoxynojirimycin (IC = 192.0 μM) and acarbose (IC = 707.9 μM). Compounds 7 and 10 have relatively higher therapeutic indices (CC/IC = 17 and 10, respectively), representing potential promising leads. The enzyme kinetic studies of compounds 1 and 24 showed a non-competitive inhibition on α-glucosidase with Ki values of 1.50 and 3.45 μM, respectively. Additionally, compounds 14, 21, 26, 29, 32, 35, and 37 were found to exhibit strong cytotoxicity against three tumor cell lines A549 (lung adenocarcinoma epithelial), HeLa (cervical carcinoma), and HepG2 (hepatocellular liver carcinoma) with IC values ranging from 0.15 to 5.26 μM. Further study indicated that 32 could induce S-phase arrest in the cell cycle progression.
特非醇（1）是一种天然丰富的对三联苯代谢物，从珊瑚来源的真菌棘孢曲霉中分离出来，同时分离出四个天然类似物 2-5。为了评估它们的效力和选择性，设计并半合成了一系列 1 的新型衍生物。评估了它们对α-葡萄糖苷酶的抑制、细胞毒性和抗菌活性。化合物 1、3、4、7、8、10、11、14、15、21、23、24、29、39 和 40 对α-葡萄糖苷酶表现出显著的抑制活性，IC 值为 4.79-15 μM，比阳性对照物 1-脱氧野尻霉素（IC = 192.0 μM）和阿卡波糖（IC = 707.9 μM）更强。化合物 7 和 10 具有相对较高的治疗指数（CC/IC = 17 和 10），代表有潜力的潜在先导化合物。化合物 1 和 24 的酶动力学研究表明，对 α-葡萄糖苷酶具有非竞争性抑制作用，Ki 值分别为 1.50 和 3.45 μM。此外，化合物 14、21、26、29、32、35 和 37 被发现对三种肿瘤细胞系 A549（肺腺癌细胞上皮）、HeLa（宫颈癌）和 HepG2（肝癌）具有很强的细胞毒性，IC 值范围为 0.15 至 5.26 μM。进一步的研究表明，32 可诱导细胞周期进展中的 S 期停滞。
