Green Synthesis of Tetrahydropyrazino[2,1-a:5,4-a']diisoquinolines as SARS-CoV-2 Entry Inhibitors

  • ACS Omega. 2024 Dec 20;10(1):1164-1176. doi: 10.1021/acsomega.4c08640.
Sowndarya Palla  1 ,  Srinivasa Rao Palla  2  3 ,  Jia-Jin Liu  2 ,  Tai-Ling Chao  4 ,  Ting-Hui Lee  5 ,  Veerababurao Kavala  1 ,  I-Chen Liu  2 ,  Lily Hui-Ching Wang  6 ,  Sui-Yuan Chang  4  7 ,  Ching-Fa Yao  1 ,  Po-Huang Liang  8  2  3
Affiliations
  • 1. Department of Chemistry, National Taiwan Normal University, Taipei 11677, Taiwan.
  • 2. Institute of Biochemical Sciences, National Taiwan University, Taipei 10617, Taiwan.
  • 3. Taiwan International Graduate Program, Academia Sinica, Taipei 11529, Taiwan.
  • 4. Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University, Taipei 10048, Taiwan.
  • 5. Department of Life Science, National Tsing Hua University, Hsinchu 30013, Taiwan.
  • 6. Institute of Molecular and Cellular Biology, National Tsing Hua University, Hsinchu 30013, Taiwan.
  • 7. Department of Laboratory Medicine, National Taiwan University Hospital, Taipei 10002, Taiwan.
  • 8. Institute of Biological Chemistry, Academia Sinica, Taipei 11529, Taiwan.
PMID: 39829498 DOI: 10.1021/acsomega.4c08640
Abstract

A class of tetrahydropyrazino[2,1-a:5,4-a']diisoquinoline derivatives were synthesized under environmentally friendly conditions using water as the solvent. The 3-D structures of some synthesized compounds were determined by X-ray diffraction. Since naturally occurring Isoquinoline Alkaloids have significant Antiviral activities against a wide range of viruses, including coronaviruses, the synthesized compounds were assayed for their inhibitory activities against SARS-CoV-2. Our results showed that the active compounds 50 and 96 blocked the delta SARS-CoV-2 entry into VeroE6 cells to display EC50 of 26.5 ± 6.9 and 17.0 ± 3.7 μM, respectively, by inhibiting the interaction between SARS-CoV-2 Spike's receptor binding domain (RBD) and human receptor angiotensin-converting enzyme 2 (ACE2), and CC50 greater than 100 μM. This study provides a green synthesis method of tetrahydropyrazinodiisoquinoline for Antiviral or Other applications.

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