Total synthesis of dryocrassin ABBA and its analogues with potential inhibitory activity against drug-resistant neuraminidases

Bioorg Med Chem. 2019 Sep 1;27(17):3846-3852. doi: 10.1016/j.bmc.2019.07.013.

Bo Hou ¹, Ze Liu ², Xiao-Bei Yang ¹, Wen-Fei Zhu ³, Jin-Yu Li ¹, Liu Yang ⁴, Fu-Cai Reng ¹, Yong-Feng Lv ¹, Jiang-Miao Hu ⁵, Guo-Yang Liao ⁶, Jun Zhou ⁷

Affiliations

1 State Key Laboratory of Phytochemistry and Plant Resources in West China, and Yunnan Key Laboratory of Natural Medicinal Chemistry, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, People' s Republic of China; University of Chinese Academy of Sciences, Beijing 100049, People's Republic of China.
2 The Fifth Department of Biological Products, Institute of Medical Biology, Chinese Academy of Medical Science and Peking Union Medical College, Kunming, People's Republic of China.
3 National Institute for Viral Disease Control and Prevention, Chinese Centre for Disease Control and Prevention, China.
4 State Key Laboratory of Phytochemistry and Plant Resources in West China, and Yunnan Key Laboratory of Natural Medicinal Chemistry, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, People' s Republic of China.
5 State Key Laboratory of Phytochemistry and Plant Resources in West China, and Yunnan Key Laboratory of Natural Medicinal Chemistry, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, People' s Republic of China. Electronic address: hujiangmiao@mail.kib.ac.cn.
6 The Fifth Department of Biological Products, Institute of Medical Biology, Chinese Academy of Medical Science and Peking Union Medical College, Kunming, People's Republic of China. Electronic address: mybelieze@126.com.
7 State Key Laboratory of Phytochemistry and Plant Resources in West China, and Yunnan Key Laboratory of Natural Medicinal Chemistry, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, People' s Republic of China. Electronic address: jzhou@mail.kib.ac.cn.

PMID: 31324565 DOI: 10.1016/j.bmc.2019.07.013

Abstract

The stems of Dryopteris crassirhizoma, one of the main components of Lianhua-Qingwen Formula (LQF) was traditionally used for heat-clearing and detoxifying. Dryocrassin ABBA is a key Antiviral component in the herbal medicine while the compound is hard to get in large amounts with the features of homologous compounds, polyphenol groups, and low contents. Therefore, the present work aims to seek influenza H7N9 virus inhibitors from natural source by synthesis of dryocrassin ABBA and its analogues. As a result, total synthesis of the compound was achieved in nine steps with an over-all yield of 4.6%. Neuraminidases (NAs) inhibitory activities of the synthesized product and its analogues were evaluated afterward. Comparing with the positive control, OSV (9.6 μM), it was very exciting that dryocrassin ABBA and its analogues (b5 and e2) showed better NAs inhibitory activity against Anhui H7N9 with IC₅₀ values of 3.6 μM, 2.5 μM and 1.6 μM. For the highly resistant Shanghai N9, these compounds can also show medium inhibitory activities. Docking results indicated the direct interaction of synthesized 3 hits with the key K294 by hydrogen bonds, but no direct interaction of OSV with the key K294 was observed in Shanghai N9. This study suggested that dryocrassin ABBA and its analogues especially AB, which consisted of polyphenol groups may have beneficial effects on treating avian influenza H7N9 virus.

Keywords

Anhui H7N9; Dryocrassin ABBA; Neuraminidase; Shanghai H7N9; Total synthesis.

Name
Email *

	Sorry, but the email address you supplied was invalid.