PBDE: Structure-Activity Studies for the Inhibition of Hepatitis C Virus NS3 Helicase

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

doi:10.3390/molecules19044006

Molecules (Apr 2014)

PBDE: Structure-Activity Studies for the Inhibition of Hepatitis C Virus NS3 Helicase

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

Affiliations

Kazi Abdus Salam: Radioisotope Center, The University of Tokyo, 2-11-16 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan
Atsushi Furuta: Department of Life Science and Medical Bioscience, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan
Naohiro Noda: Department of Life Science and Medical Bioscience, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan
Satoshi Tsuneda: Department of Life Science and Medical Bioscience, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan
Yuji Sekiguchi: Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), 1-1-1 Higashi, Tsukuba, Ibaraki 305-8566, Japan
Atsuya Yamashita: Department of Microbiology, Graduate School of Medicine and Engineering, University of Yamanashi, 1110 Shimokato, Chuo-shi, Yamanashi 409-3898, Japan
Kohji Moriishi: Department of Microbiology, Graduate School of Medicine and Engineering, University of Yamanashi, 1110 Shimokato, Chuo-shi, Yamanashi 409-3898, Japan
Masamichi Nakakoshi: Faculty of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan
Hidenori Tani: Research Institute for Environmental Management Technology, National Institute of Advanced Industrial Science and Technology (AIST), 16-1, Onogawa, Tsukuba, Ibaraki 305-8569, Japan
Sona Rani Roy: Department of Chemistry, Biology and Marine Science, University of the Ryukyus, Nishihara, Okinawa 903-0213, Japan
Junichi Tanaka: Department of Chemistry, Biology and Marine Science, University of the Ryukyus, Nishihara, Okinawa 903-0213, Japan
Masayoshi Tsubuki: Institute of Medical Chemistry, Hoshi University, Ebara 2-4-41, Shinagawa-ku, Tokyo 142-8501, Japan
Nobuyoshi Akimitsu: Radioisotope Center, The University of Tokyo, 2-11-16 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan

DOI: https://doi.org/10.3390/molecules19044006
Journal volume & issue: Vol. 19, no. 4
pp. 4006 – 4020

Abstract

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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.

Published in Molecules

ISSN: 1420-3049 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Science: Chemistry: Organic chemistry
Website: http://www.mdpi.com/journal/molecules

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