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Bioorg Chem
. 2025 Jul 21:163:108785.
doi: 10.1016/j.bioorg.2025.108785. Online ahead of print. Discovery of tetrasubstituted tetrahydropyrimidines as novel inhibitors against influenza a virus
Zesheng Huang 1 , Zhixuan Chen 1 , Xiaoyi Qin 1 , Qiuhua Zhu 2 , Jie Yang 3
Affiliations
A series of tetra-substituted tetrahydropyrimidines (TTHPs 501-528) was designed and synthesized by an efficient one-pot four-component reaction (4CR) to study their bioactivities as novel inhibitors against influenza A virus (H1N1) infection. The structure-activity relationship (SAR) indicates that the antiviral activities of TTHPs mainly depend on the combination of substituents, and three TTHPs (512, 513, and 521) show potent antiviral activities, with IC₅₀ values equal to 1.46, 5.09 and 4.06 μM, respectively. Furthermore, the mechanism of TTHP 512 against influenza virus A was investigated through western blotting, qRT-PCR, and an immunofluorescence assay. The primary mechanism study indicates that the most potent TTHP 512 exerts antiviral activity by affecting virus replication. In addition, TTHP 521 shows strong aggregation-induced emission and can target endoplasmic reticulum imaging.
Keywords: Design and synthesis; Endoplasmic reticulum imaging; Influenza a virus; Multicomponent reaction; Structure-activity relationship; Tetrahydropyrimidines.
. 2025 Jul 21:163:108785.
doi: 10.1016/j.bioorg.2025.108785. Online ahead of print. Discovery of tetrasubstituted tetrahydropyrimidines as novel inhibitors against influenza a virus
Zesheng Huang 1 , Zhixuan Chen 1 , Xiaoyi Qin 1 , Qiuhua Zhu 2 , Jie Yang 3
Affiliations
- PMID: 40714481
- DOI: 10.1016/j.bioorg.2025.108785
A series of tetra-substituted tetrahydropyrimidines (TTHPs 501-528) was designed and synthesized by an efficient one-pot four-component reaction (4CR) to study their bioactivities as novel inhibitors against influenza A virus (H1N1) infection. The structure-activity relationship (SAR) indicates that the antiviral activities of TTHPs mainly depend on the combination of substituents, and three TTHPs (512, 513, and 521) show potent antiviral activities, with IC₅₀ values equal to 1.46, 5.09 and 4.06 μM, respectively. Furthermore, the mechanism of TTHP 512 against influenza virus A was investigated through western blotting, qRT-PCR, and an immunofluorescence assay. The primary mechanism study indicates that the most potent TTHP 512 exerts antiviral activity by affecting virus replication. In addition, TTHP 521 shows strong aggregation-induced emission and can target endoplasmic reticulum imaging.
Keywords: Design and synthesis; Endoplasmic reticulum imaging; Influenza a virus; Multicomponent reaction; Structure-activity relationship; Tetrahydropyrimidines.