Design, synthesis, antiviral bioactivities and interaction mechanisms of penta-1,4-diene-3-one oxime ether derivatives containing a quinazolin-4(3H)-one scaffold

BACKGROUND: penta-1,4-diene-3-one oxime ether and quinazolin-4(3H)-one derivatives possess favorable agricultural activities. Aiming to discover novel molecules with highly-efficient agricultural activities, a series of penta-1,4-diene-3-one oxime ether derivatives containing a quinazolin-4(3H)-one scaffold were synthesized and evaluated for their antiviral activities. RESULT: Antiviral bioassays indicated that some title compounds exhibited significant antiviral activity against tobacco mosaic virus (TMV). In particular, compounds 8c, 8j and 8k possessed appreciable curative activities against TMV in vivo, with half-maximal effective concentration (EC(50)) values of 138.5, 132.9 and 125.6 μg/mL, respectively, which are better than that of ningnanmycin (207.3 μg/mL). Furthermore, the microscale thermophoresis experiments (MST) on the interaction of compound 8k with TMV coat protein (TMV CP) showed 8k bound to TMV CP with a dissociation constant of 0.97 mmol/L. Docking studies provided further insights into the interaction of 8k with the Arg90 of TMV CP. CONCLUSIONS: Sixteen penta-1,4-diene-3-one oxime ether derivatives containing a quinazolin-4(3H)-one scaffold were designed, synthesized, and their antiviral activities against TMV were evaluated. Antiviral bioassays indicated that some target compounds exhibited remarkable antiviral activities against TMV. Furthermore, through the MST and docking studies, we can speculate that 8k inhibited the virulence of TMV by binding Arg90 in TMV CP. These results indicated that this kind of penta-1,4-diene-3-one oxime ether derivatives containing a quinazolin-4(3H)-one scaffold could be further studied as potential alternative templates in the search for novel antiviral agents. [Image: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13065-019-0547-1) contains supplementary material, which is available to authorized users.