p-Terphenyls as Anti-HSV-1/2 Agents from a Deep-Sea-Derived Penicillium sp

  • J Nat Prod. 2021 Nov 26;84(11):2822-2831. doi: 10.1021/acs.jnatprod.1c00400.
Weihao Chen  1  2 ,  Jiawen Zhang  3 ,  Xin Qi  1 ,  Kai Zhao  1 ,  Xiaoyan Pang  1 ,  Xiuping Lin  1  4  5 ,  Shengrong Liao  1  4  5 ,  Bin Yang  1  4  5 ,  Xuefeng Zhou  1  4  5 ,  Shuwen Liu  3 ,  Junfeng Wang  1  4  5 ,  Xingang Yao  3 ,  Yonghong Liu  1  4  2  5
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, People's Republic of China.
  • 2. University of Chinese Academy of Sciences, 19 Yuquan Road, Beijing 100049, People's Republic of China.
  • 3. State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, People's Republic of China.
  • 4. Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou), Guangzhou 511458, People's Republic of China.
  • 5. Sanya Institute of Oceanology, SCSIO, Yazhou Scientific Bay, Sanya 572000, People's Republic of China.
PMID: 34766503 DOI: 10.1021/acs.jnatprod.1c00400
Abstract

Guided by Global Natural Products Social molecular networking, two p-terphenyl derivatives and one 4,5-diphenyl-2-pyrone analogue, peniterphenyls A-C (1-3), together with five known p-terphenyl derivatives (4-8) and sulochrin (9), were obtained from a deep-sea-derived Penicillium sp. SCSIO41030. Their structures were elucidated using extensive NMR spectroscopic and HRESIMS data and by comparing the information with literature data. Peniterphenyl B (2) represented the first reported natural product possessing a 4,5-diphenyl-substituted 2-pyrone derivative. The p-terphenyl derivatives displayed inhibitory activities against HSV-1/2 with EC50 values ranging from 1.4 ± 0.6 to 9.3 ± 3.7 μM in Vero cells, which showed that they possessed Antiviral activities with low cytotoxicity, superior to the current clinical drug acyclovir (EC50 3.6 ± 0.7 μM). Peniterphenyl A (1) inhibited HSV-1/2 virus entry into cells and may block HSV-1/2 Infection through direct interaction with virus envelope glycoprotein D to interfere with virus adsorption and membrane fusion, and thus differs from the nucleoside analogues such as acyclovir. Our study indicated peniterphenyl A (1) could be a promising lead compound against HSV-1/2.

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