Inactivating Activities and Mechanism of Imidazo[1,2-]pyrimidin-5(6)-one Nucleoside Derivatives Incorporating a Sulfonamide Scaffold.

Twenty-eight imidazo[1,2-]pyrimidin-5(6)-one nucleoside derivatives incorporating a sulfonamide scaffold with preferable inactivating activities on pepper mild mottle virus (PMMoV) were designed and synthesized. Then, compound with illustrious inactivating activity against PMMoV was received on the basis of the three-dimensional quantitative structure-activity relationship (3D-QSAR) model, with the EC of 11.4 μg/mL, which was superior to ningnanmycin (65.8 μg/mL) and template molecule (15.3 μg/mL). Furthermore, (1) transmission electron microscopy (TEM) indicated that could cause severe fracture of virions; (2) microscale thermophoresis (MST) and molecular docking further demonstrated that had faintish binding affinities with PMMoV CP ( = 202.84 μM), PMMoV CP ( = 141.57 μM), and PMMoV CP ( = 332.06 μM) compared to PMMoV CP ( = 4.76 μM); and (3) western blot and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) results of pCB-GFP-PMMoV CP, pCB-GFP-PMMoV CP, and pCB-GFP-PMMoV CP were consistent with MST and confocal. In brief, the above results indicated that the amino acids at positions 62 and 144 of PMMoV CP might be the key amino acid sites of acted on.