多溴二苯醚：针对丙型肝炎病毒NS3解旋酶抑制作用的构效关系研究

Salam Kazi Abdus, Furuta Atsushi, Noda Naohiro, Tsuneda Satoshi, Sekiguchi Yuji, Yamashita Atsuya, Moriishi Kohji, Nakakoshi Masamichi, Tani Hidenori, Roy Sona Rani, Tanaka Junichi, Tsubuki Masayoshi, Akimitsu Nobuyoshi

Radioisotope Center, The University of Tokyo, 2-11-16 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.

Department of Life Science and Medical Bioscience, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan.

Molecules. 2014 Apr 2;19(4):4006-20. doi: 10.3390/molecules19044006.

The helicase portion of the hepatitis C virus nonstructural protein 3 (NS3) is considered one of the most validated targets for developing direct acting antiviral agents. We isolated polybrominated diphenyl ether (PBDE) 1 from a marine sponge as an NS3 helicase inhibitor. In this study, we evaluated the inhibitory effects of PBDE (1) on the essential activities of NS3 protein such as RNA helicase, ATPase, and RNA binding activities. The structure-activity relationship analysis of PBDE (1) against the HCV ATPase revealed that the biphenyl ring, bromine, and phenolic hydroxyl group on the benzene backbone might be a basic scaffold for the inhibitory potency.

丙型肝炎病毒非结构蛋白3（NS3）的解旋酶部分被认为是开发直接作用抗病毒药物最有效的靶点之一。我们从一种海洋海绵中分离出多溴二苯醚（PBDE）1作为NS3解旋酶抑制剂。在本研究中，我们评估了PBDE（1）对NS3蛋白基本活性的抑制作用，如RNA解旋酶、ATP酶和RNA结合活性。PBDE（1）对HCV ATP酶的构效关系分析表明，苯骨架上的联苯环、溴和酚羟基可能是抑制效力的基本支架。