Li Peng, Wang Shijie, Wang Huiqin, Yan Hong
Beijing Key Laboratory of Environmental and Viral Oncology, College of Life Science and Bioengineering, Beijing University of Technology.
Biol Pharm Bull. 2019;42(2):261-267. doi: 10.1248/bpb.b18-00705.
A series of tetraethyl 2,4,8,10-tetramethyl-6,12-diaryl-3,9-dioxahexacyclo[6.4.0.02,7.04,11.05,10]dodecane-1,5,7,11-tetracarboxylates (simplified as 3,9-dioxatetraasteranes) with C-symmetric structural characteristics were synthesized through the [2 + 2] photocycloaddition of the diethyl 2,6-dimethyl-4-aryl-4H-pyran-3,5-dicarboxylates. Besides, their anti-human immunodeficiency virus (HIV)-1 activities were evaluated by enzyme-linked immunosorbent assay (ELISA) assay against HIV-1 (IIIB) replication in MT-4 cell culture. The result showed that the tested compounds exhibited potential activates with IC values less than 110 nM. Furthermore, docking study was carried out to study the binding mode of these compounds. The results indicated that the overall orientation of the inhibitors in the active site were similar to that of the cyclic urea AHA001 and a hydrogen bond with the protein residues might play a crucial role in their anti-HIV-1 activities. Such results will provide a theoretical foundation for further investigations on the biological activity of 3,9-dioxatetraasteranes.
通过2,6-二甲基-4-芳基-4H-吡喃-3,5-二羧酸二乙酯的[2+2]光环化加成反应，合成了一系列具有C对称结构特征的2,4,8,10-四甲基-6,12-二芳基-3,9-二氧杂六环[6.4.0.02,7.04,11.05,10]十二烷-1,5,7,11-四羧酸四乙酯（简称为3,9-二氧杂四阿斯他汀）。此外，通过酶联免疫吸附测定（ELISA）法评估了它们对MT-4细胞培养中HIV-1（IIIB）复制的抗人免疫缺陷病毒（HIV）-1活性。结果表明，所测试的化合物表现出潜在活性，IC值小于110 nM。此外，进行了对接研究以研究这些化合物的结合模式。结果表明，抑制剂在活性位点的总体取向与环脲AHA001相似，并且与蛋白质残基的氢键可能在其抗HIV-1活性中起关键作用。这些结果将为进一步研究3,9-二氧杂四阿斯他汀的生物活性提供理论基础。
