2. Academic Validation
  3. Design, synthesis, and biological evaluation of a series of new anthraquinone derivatives as anti-ZIKV agents

Design, synthesis, and biological evaluation of a series of new anthraquinone derivatives as anti-ZIKV agents

  • Eur J Med Chem. 2023 Oct 5;258:115620. doi: 10.1016/j.ejmech.2023.115620.
Yujia Zhu 1,  Jianchen Yu 2,  Tao Chen 3,  Wenbin Liu 4,  Yun Huang 5,  Junsen Li 3,  Bingzhi Zhang 6,  Ge Zhu 7,  Zhenjian He 8,  Yuhua Long 9,  Jie Yuan 10
Affiliations

Affiliations

  • 1 School of Public Health, Sun Yat-sen University, Guangzhou, 510080, Guangdong, China. Electronic address: [email protected].
  • 2 School of Chemistry, Guangzhou Key Laboratory of Analytical Chemistry for Biomedicine, South China Normal University, Guangzhou, 510006, China; Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou, 510080, China. Electronic address: [email protected].
  • 3 School of Chemistry, Guangzhou Key Laboratory of Analytical Chemistry for Biomedicine, South China Normal University, Guangzhou, 510006, China.
  • 4 School of Chemistry, Guangzhou Key Laboratory of Analytical Chemistry for Biomedicine, South China Normal University, Guangzhou, 510006, China. Electronic address: [email protected].
  • 5 School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China.
  • 6 School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510006, China. Electronic address: [email protected].
  • 7 Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China. Electronic address: [email protected].
  • 8 School of Public Health, Sun Yat-sen University, Guangzhou, 510080, Guangdong, China; Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou, 510080, China. Electronic address: [email protected].
  • 9 School of Chemistry, Guangzhou Key Laboratory of Analytical Chemistry for Biomedicine, South China Normal University, Guangzhou, 510006, China. Electronic address: [email protected].
  • 10 School of Public Health, Sun Yat-sen University, Guangzhou, 510080, Guangdong, China; Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China. Electronic address: [email protected].
PMID: 37421888 DOI: 10.1016/j.ejmech.2023.115620
Abstract

The major severe complications linked to Zika virus (ZIKV) cause the global public health problems, including microcephaly and other congenital abnormalities in newborns, and Guillain-Barré syndrome, meningoencephalitis, multi-organ failure in adults. However, neither approved vaccines nor drugs are available for ZIKV. In this study, we describe the design, synthesis and the anti-ZIKV activities of a series of anthraquinone analogs. Most of the newly synthesized compounds demonstrated moderate to excellent potency against ZIKV. Among all, compound 22, showed the most potent anti-ZIKV activity (EC50 value from 1.33 μM to 5.72 μM) with low cytotoxicity (CC50＞50 μM) in multiple cellular model. Importantly, 22 significantly improved the survival of ZIKV-infected mice (IFNAR1-/-), alleviated ZIKV-associated pathological damages and suppressed the excessive inflammatory response and Pyroptosis induced by ZIKV in vivo and in vitro. Furthermore, the molecular docking simulation analysis and the surface plasmon resonance results demonstrated the direct binding between 22 and ZIKV RdRp, and the mechanistic study revealed that 22 suppressed viral RNA synthesis by ZIKV NS5 in cells. Taken together, this study highlights that 22 may be a novel anti-ZIKV drug candidate and provides treatment options for ZIKV-associated diseases.

Keywords

Anthraquinones; Antiviral agent; In vitro; In vivo; RdRp inhibitor; ZIKV.

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