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  3. Discovery of a novel anti-osteoporotic agent from marine fungus-derived structurally diverse sirenins

Discovery of a novel anti-osteoporotic agent from marine fungus-derived structurally diverse sirenins

  • Eur J Med Chem. 2023 Dec 19:265:116068. doi: 10.1016/j.ejmech.2023.116068.
Jian Cai 1,  Li Gao 2,  Yue Wang 3,  Yuanteng Zheng 2,  Xiuling Lin 4,  Pingzheng Zhou 4,  Chunmei Chen 5,  Kechun Liu 2,  Lan Tang 4,  Yonghong Liu 1,  Yanhui Tan 6,  Meng Jin 7,  Xuefeng Zhou 8
Affiliations

Affiliations

  • 1 CAS Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou, 510301, China; University of Chinese Academy of Sciences, Beijing, 100049, China.
  • 2 Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Ji'nan, 250103, China; Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province, Ji'nan, 250103, China.
  • 3 State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin, 541001, China.
  • 4 School of Pharmaceutical Sciences, Guangdong Provincial Key Laboratory of New Drug Screening, Southern Medical University, Guangzhou, 510515, China.
  • 5 CAS Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou, 510301, China.
  • 6 State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin, 541001, China. Electronic address: tyh533@126.com.
  • 7 Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Ji'nan, 250103, China; Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province, Ji'nan, 250103, China. Electronic address: mjin1985@hotmail.com.
  • 8 CAS Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou, 510301, China; University of Chinese Academy of Sciences, Beijing, 100049, China. Electronic address: xfzhou@scsio.ac.cn.
PMID: 38141284 DOI: 10.1016/j.ejmech.2023.116068
Abstract

Thirteen new sirenin derivatives named eupenicisirenins C-O (1-13), along with a biosynthetically related known one (14), were isolated from the mangrove sediment-derived fungus Penicillium sp. SCSIO 41410. The structures, which possessed a rare cyclopropane moiety, were confirmed by extensive analyses of the spectroscopic data, quantum chemical calculations, and X-ray diffraction. Among them, eupenicisirenin C (1) exhibited the strongest NF-κB inhibitory activities, as well as suppressing effects on cGAS-STING pathway. Moreover, 1 showed the significant inhibitory effect on RANKL-induced osteoclast differentiation in bone marrow macrophages cells, and also displayed the therapeutic potential on prednisolone-induced zebrafish osteoporosis. Transcriptome analysis and the following verification tests suggested that its anti-osteoporotic mechanism is related to the extracellular matrix receptor interaction-related pathways. This study provided a promising marine-derived anti-osteoporotic agent for the treatment of skeletal disease.

Keywords

Anti-osteoporosis; Eupenicisirenins; Marine fungus; Sirenins.

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