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

Abstract

Background penta-1,4-diene-3-one oxime ether and quinazolin-4(3 H )-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(3 H )-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(3 H )-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(3 H )-one scaffold could be further studied as potential alternative templates in the search for novel antiviral agents. Electronic supplementary material The online version of this article (10.1186/s13065-019-0547-1) contains supplementary material, which is available to authorized users.

Peer Review #1 of "Synthesis and biological activity of 1,4-pentadien-3-one derivatives containing triazine scaffolds (v0.1)"

“…A synthetic route to 1,4-pentadien-3-one derivatives containing a triazine moiety was designed and shown in Figure 5. According to previously reported methods (Chen et al, 2019;Tang et al, 2019;, Gan et al, 2017), intermediates 1 and 2 could be obtained. Using benzyl, biacetyl and thio-semicarbazide as the initial materials in acetic acid and water was stirred at 100-110 o C for 6-8 h to obtain the intermediate 3 (Tang et al, 2019).…”

“…According to previously reported methods (Chen et al, 2019;Tang et al, 2019;, Gan et al, 2017), intermediates 1 and 2 could be obtained. Using benzyl, biacetyl and thio-semicarbazide as the initial materials in acetic acid and water was stirred at 100-110 o C for 6-8 h to obtain the intermediate 3 (Tang et al, 2019). Tang et al, 2019;Zhang et al, 2017).This test method is provided in the Supporting Information.…”

“…Notably, Chen et al verified the anti-TMV mechanism of 1,4-pentadien-3-one derivatives (Figure 2), and found 5-position of 1,4-pentadien-3-one nucleus had played a key role in antiviral activities (Chen et al, 2019). In addition, triazine scaffold has been associated with diversified pharmacological activities (Irannejad et al, 2010), such as antioxidant (Khoshneviszadeh et al, 2016), antithrombotic (Tamboli et al, 2015), antiplatelet (Konno et al,1993), anticancer (Fu et al, 2017, thromboxane synthetase inhibition (Monge et al, 2010), antimalarial (Tamboli et al, 2015 Manuscript to be reviewed Chemistry Journals Analytical, Inorganic, Organic, Physical, Materials Science inhibition (Wang et al, 2016), antiviral and antibacterial activities (Tang et al, 2019). Recently, it was found that the heterocyclic nitrogen of the triazine derivatives had tremendous applications in the development of novel agricultural bactericides and virucides (Zhang et al, 2018).…”

“…Using benzyl, biacetyl and thio-semicarbazide as the initial materials in acetic acid and water was stirred at 100-110 o C for 6-8 h to obtain the intermediate 3 (Tang et al, 2019). Tang et al, 2019;Zhang et al, 2017).This test method is provided in the Supporting Information.…”

“…Using N. tabacun L. leaves under the same age as that of test subjects, the curative, protective and inactivation activities against TMV (in vivo) at a concentration of 500 μg/mL were evaluated by the half-leaf blight spot method (Chen et al, 2019).This test method is provided in the Supporting Information.…”