Neuroprotective azaphilones from a deep-sea derived fungus Penicillium sp. SCSIO41030

Weihao Chen; Jiahui Jiang; Xiaoyan Pang; Yingying Song; Zhiyou Yang; Junfeng Wang; Yonghong Liu

doi:10.1039/d4ob00586d

Neuroprotective azaphilones from a deep-sea derived fungus Penicillium sp. SCSIO41030

Org Biomol Chem. 2024 Jun 5;22(22):4521-4527. doi: 10.1039/d4ob00586d.

Authors

Weihao Chen^{1

2}, Jiahui Jiang³, Xiaoyan Pang¹, Yingying Song^{1

2}, Zhiyou Yang³, Junfeng Wang^{1

2

4}, Yonghong Liu^{1

2

4}

Affiliations

¹ CAS Key Laboratory of Tropical Marine Bio-resources and Ecology/Guangdong Key Laboratory of Marine Materia Medica/Innovation Academy of South China Sea Ecology and Environmental Engineering, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, China. wangjunfeng@scsio.ac.cn.
² University of Chinese Academy of Sciences, 19 Yuquan Road, Beijing 100049, China.
³ College of Food Science and Technology, Guangdong Provincial Key Laboratory of Aquatic Product Processing and Safety, Guangdong Province Engineering Laboratory for Marine Biological Products, Guangdong Provincial Engineering Technology Research Center of Seafood, Key Laboratory of Advanced Processing of Aquatic Product of Guangdong Higher Education Institution, Guangdong Ocean University, Zhanjiang 524088, China. zyyang@gdou.edu.cn.
⁴ Sanya Institute of Marine Ecology and Engineering, Yazhou Scientific Bay, Sanya 572000, China.

PMID: 38752482
DOI: 10.1039/d4ob00586d

Abstract

Ten azaphilones including one pair of new epimers and three new ones, penineulones A-E (1-5) with the same structural core of angular deflectin, were obtained from a deep-sea derived Penicillium sp. SCSIO41030 fermented on a liquid medium. Their structures including absolute configurations were elucidated using chiral-phase HPLC analysis, extensive NMR spectroscopic and HRESIMS data, ECD and NMR calculations, and by comparing NMR data with literature data. Biological assays showed that the azaphilones possessed no antitumor and anti-viral (HSV-1/2) activities at concentrations of 5.0 μM and 20 μM, respectively. In addition, azaphilones 8 and 9 showed neuroprotective effects against Aβ_25-35-induced neurotoxicity in primary cultured cortical neurons at a concentration of 10 μM. Azaphilones 8 and 9 dramatically promoted axonal regrowth against Aβ_25-35-induced axonal atrophy. Our study indicated that azaphilones could be promising lead compounds for neuroprotection.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amyloid beta-Peptides / antagonists & inhibitors
Amyloid beta-Peptides / metabolism
Amyloid beta-Peptides / pharmacology
Animals
Benzopyrans* / chemistry
Benzopyrans* / isolation & purification
Benzopyrans* / pharmacology
Humans
Molecular Structure
Neurons / drug effects
Neuroprotective Agents* / chemistry
Neuroprotective Agents* / isolation & purification
Neuroprotective Agents* / pharmacology
Penicillium* / chemistry
Peptide Fragments / chemistry
Peptide Fragments / pharmacology
Pigments, Biological / chemistry
Pigments, Biological / isolation & purification
Pigments, Biological / pharmacology

Substances

azaphilone
Neuroprotective Agents
Benzopyrans
Amyloid beta-Peptides
Pigments, Biological
amyloid beta-protein (25-35)
Peptide Fragments