Diversity-oriented synthesis of marine sponge derived hyrtioreticulins and their anti-inflammatory activities

Bo-Ru Chen; Cheng-Long Gao; Jin Liu; Yue-Wei Guo; Jian-Lan Jiang; Tao Pang; Xu-Wen Li

doi:10.1016/S1875-5364(22)60155-9

Diversity-oriented synthesis of marine sponge derived hyrtioreticulins and their anti-inflammatory activities

Chin J Nat Med. 2022 Jan;20(1):74-80. doi: 10.1016/S1875-5364(22)60155-9.

Authors

Bo-Ru Chen¹, Cheng-Long Gao², Jin Liu³, Yue-Wei Guo⁴, Jian-Lan Jiang⁵, Tao Pang⁶, Xu-Wen Li⁷

Affiliations

¹ School of Chemical Engineering and Technology, Tianjin University, Tianjin 300350, China; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
² State Key Laboratory of Natural Medicines, New Drug Screening Center, China Pharmaceutical University, Nanjing 210009, China.
³ State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
⁴ State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; Open Studio for Druggability Research of Marine Natural Products, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266237, China.
⁵ School of Chemical Engineering and Technology, Tianjin University, Tianjin 300350, China. Electronic address: jljiang@tju.edu.cn.
⁶ State Key Laboratory of Natural Medicines, New Drug Screening Center, China Pharmaceutical University, Nanjing 210009, China. Electronic address: tpang@cpu.edu.cn.
⁷ State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; Open Studio for Druggability Research of Marine Natural Products, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266237, China. Electronic address: xwli@simm.ac.cn.

PMID: 35101252
DOI: 10.1016/S1875-5364(22)60155-9

Abstract

Diversity-oriented synthesis is aimed to increase the chemical diversity of target natural products for extensive biological activity evaluation. Indole ring is an important functional group in a large number of drugs and other biologically active agents, and indole-containing natural products have been frequently isolated from marine sources in recent years. In this paper, a series of indole-containing marine natural hyrtioreticulin derivatives, including 19 new ones, were designed, synthesized through a key Pictet-Spengler reaction, and evaluated for their inflammation related activity. Compound 13b displayed the most promising activity by inhibiting TNF-α cytokine release with an inhibitory rate of 92% at a concentration of 20 μmol·L^-1. A preliminary structure-activity relationship analysis was also discussed. This research may throw light on the discovery of marine indole alkaloid derived anti-inflammatory drug leads.

Keywords: Hyrtioreticulin; Indole alkaloid; Inflammation; Pictet-Spengler reaction.

MeSH terms

Animals
Anti-Inflammatory Agents / pharmacology
Biological Products* / pharmacology
Indole Alkaloids / pharmacology
Porifera*
Structure-Activity Relationship

Substances

Anti-Inflammatory Agents
Biological Products
Indole Alkaloids