Synthesis of 4H‑Pyrazolo[3,4‑d]pyrimidin-4-one Hydrazine Derivatives as a Potential Inhibitor for the Self-Assembly of TMV Particles

• Published in: Journal of agricultural and food chemistry Vol. 72; no. 6; pp. 2879 - 2887
• Main Authors: Wang, Ya, Guo, Shengxin, Sun, Wei, Tu, Hong, Tang, Yao, Xu, Ying, Guo, Renjiang, Zhao, Zhichao, Yang, Zhaokai, Wu, Jian
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 14.02.2024; Amer Chemical Soc
• Subjects: Agricultural and Environmental Chemistry; Agriculture; Agriculture, Multidisciplinary; Chemistry; Chemistry, Applied; Food Science & Technology; Life Sciences & Biomedicine; Physical Sciences; Science & Technology; synthesis; self-assembly; hydrazine; antiviral activity; inhibitor; 4H-pyrazolo[3,4-d]pyrimidin-4-one; INSECTICIDAL ACTIVITIES; DESIGN; COAT PROTEIN
• ISSN: 0021-8561; 1520-5118
• DOI: 10.1021/acs.jafc.3c05334

Tobacco mosaic virus coat protein (TMV-CP), as a potential target for the development of antiviral agents, can assist in the long-distance movement of viruses and plays an extremely important role in virus replication and propagation. This work focuses on the synthesis and the action mechanism of novel 4H-pyrazolo­[3,4-d] pyrimidin-4-one hydrazine derivatives. The synthesized compounds exhibited promising antiviral activity on TMV. Specifically, compound G2 exhibited high inactivating activity (93%) toward TMV, slightly better than commercial reagent NNM (90%). The action of mechanism was further explored by employed molecular docking, molecular dynamics simulation, microscale thermophoresis, qRT-PCR, and transmission electron microscopy. Results indicated that G2 had the capability to interact with amino acid residues such as Trp352, Tyr139, and Asn73 in the active pocket of TMV-CP, creating strong hydrophobic interactions and thus obstructing the virus’s self-assembly.