Design, Synthesis, and Antiviral Evaluation of Novel 3,4-Dihydropyrimidin-2(1 H)-one Derivatives

  • Microorganisms. 2026 May 28;14(6):1220. doi: 10.3390/microorganisms14061220.
Chen Yao  1  2  3 ,  Zhi-Cheng Li  1  2  3 ,  Ruo-Hang Li  1  2  3 ,  Peng-Xiang Liu  1  2  3 ,  Hong-Yun Yang  1  2  3 ,  Hang Liu  1  2  3 ,  Bo Ding  1  2  3 ,  Heng Wang  1  2  3 ,  He-Ping Li  1  2  3 ,  Yue-Ying Wang  1  2  3 ,  Sheng-Li Ming  1  2  3 ,  Li-Jun Shi  4 ,  Meng-Di Wang  5
Affiliations
  • 1. College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, China.
  • 2. Key Laboratory of Animal Biochemistry and Nutrition, Ministry of Agriculture and Rural Affairs, Zhengzhou 450046, China.
  • 3. Key Laboratory of Animal Growth and Development of Henan Province, Henan Agricultural University, Zhengzhou 450046, China.
  • 4. College of Sciences, Henan Agricultural University, Zhengzhou 450046, China.
  • 5. College of Life Sciences, Henan University of Animal Husbandry and Economy, Zhengzhou 450046, China.
PMID: 42354845 DOI: 10.3390/microorganisms14061220
Abstract

The 3,4-dihydropyrimidin-2(1H)-one (DHPM) scaffold possesses diverse biological activities and chemical tunability, allowing structural modifications to modulate Antiviral, Anticancer, and anti-inflammatory effects. In this study, a series of DHPM derivatives with varied substituents were designed and synthesized, and their structures were characterized by 1H NMR, 13C NMR and HRMS. Their Antiviral activities against pseudorabies virus (PRV) and vesicular stomatitis virus (VSV) were evaluated. In vitro assays revealed that several compounds exhibited significant Antiviral effects, with 4bf (SI = 243.08 against PRV), 4ce (SI = 196.4 against VSV), and 4be (SI = 124.2 against PRV; SI = 181.1 against VSV) showing the most potent activity. Further studies demonstrated effective inhibition of viral titers, and Western blot and qRT-PCR analyses confirmed downregulation of Viral Proteins and related genes. Cytotoxicity tests indicated that 4bf, 4ce, and 4be had CC50 values of 270.0, 147.1, and 190.9 μg/mL, respectively, suggesting favorable safety profiles. In vivo experiments showed that 4bf, without affecting normal growth, alleviated PRV-induced pulmonary inflammation and tissue damage, and improved survival in mice. Taken together, DHPM-based compounds demonstrate promising potential as candidate Antiviral agents, warranting further development.

Keywords
4-Dihydropyrimidin-2(1H)-one (DHPM); antiviral activity; in vivo efficacy; synthesis.
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