Synthesis, Biological Activity and Action Mechanism Study of Novel Chalcone Derivatives Containing Malonate.

A series of novel chalcone malonate derivatives were synthesized and their antibacterial and antiviral activities were evaluated. All target compounds were characterized by spectral data. The results of antimicrobial bioassay showed that one compound (diethyl [3-(naphthalen-2-yl)-1-(3-nitrophenyl)-3-oxopropyl]propanedioate) showed excellent antibacterial activity against Xanthomonas oryzae pv. oryzae (Xoo), with an EC50 value of 10.2 µg/mL, which is significantly superior to bismerthiazol (71.7 µg/mL) and thiodiazole copper (97.8 µg/mL). At the same time, the mechanism of two compounds was confirmed by scanning electron microscopy. In addition, another compound (diethyl [3-(naphthalen-2-yl)-1-(4-nitrophenyl)-3-oxopropyl]propanedioate) showed significant curative activity to tobacco mosaic virus, with a value of 74.3 %, which was superior to 53.3 % of ningnanmycin. The results of microscale thermophoresis also showed that the Kd value of the combination of two compounds with the coat protein of tobacco mosaic virus was 0.211 and 0.166 µmol/L, which was better than 0.596 µmol/L of ningnanmycin. At the same time, the molecular docking of two compounds with tobacco mosaic virus-coat protein shows that the compound is well embedded in the pocket between the two subunits of tobacco mosaic virus-coat protein. These results show that chalcone derivatives containing malonate group can be considered as activators in the design of antibacterial and antiviral agents.

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 (EC50) 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.

Novel Phosphorylated Penta-1,4-dien-3-one Derivatives: Design, Synthesis, and Biological Activity.

A series of novel phosphorylated penta-1,4-dien-3-one derivatives were designed and synthesized. The structures of all title compounds were determined by ¹H-NMR, 13C-NMR, 31P-NMR, and high-resolution mass spectrometry (HRMS). Bioassay results showed that several of the title compounds exhibited remarkable antibacterial and antiviral activities. Among these, compound 3g exhibited substantial antibacterial activity against Xanthomonas oryzae pv. Oryzae (Xoo), with a 50% effective concentration (EC50) value of 8.6 µg/mL, which was significantly superior to bismerthiazol (BT) (58.8 µg/mL) and thiodiazole-copper (TC) (78.7 µg/mL). In addition, compound 3h showed remarkable protective activity against tobacco mosaic virus (TMV), with an EC50 value of 104.2 µg/mL, which was superior to that of ningnanmycin (386.2 µg/mL). Furthermore, the microscale thermophoresis and molecular docking experiments on the interaction of compounds 3h and 3j with TMV coat protein (TMV CP) were also investigated. Compounds 3h and 3j bound to TMV CP with dissociation constants of 0.028 and 0.23 µmol/L, which were better than that of ningnanmycin (0.52 µmol/L). These results suggest that novel phosphorylated penta-1,4-dien-3-one derivatives may be considered as an activator for antibacterial and antiviral agents.

Novel chalcone derivatives containing a 1,2,4-triazine moiety: design, synthesis, antibacterial and antiviral activities.

A series of novel chalcone derivatives containing the 1,2,4-triazine moiety were synthesized and their structures were confirmed by 1H NMR, 13C NMR and elemental analyses. Antiviral bioassays revealed that most of the compounds exhibited good antiviral activity against tobacco mosaic virus (TMV) at a concentration of 500 µg mL-1. The designated compound 4l was 50% effective in terms of curative and protective activities against TMV with 50% effective concentrations (EC50) of 10.9 and 79.4 µg mL-1, which were better than those of ningnanmycin (81.4 and 82.2 µg mL-1). Microscale thermophoresis (MST) also showed that the binding of compound 4l to coat protein (TMV-CP) yielded a K d value of 0.275 ± 0.160 µmol L-1, which was better than that of ningnanmycin (0.523 ± 0.250 µmol L-1). At the same time, molecular docking studies for 4l with TMV-CP (PDB code:1EI7) showed that the compound was embedded well in the pocket between the two subunits of TMV-CP. Meanwhile, compound 4a demonstrated excellent antibacterial activities against Ralstonia solanacearum (R. solanacearum), with an EC50 value of 0.1 µg mL-1, which was better than that of thiodiazole-copper (36.1 µg mL-1) and bismerthiazol (49.5 µg mL-1). The compounds act by causing folding and deformation of the bacterial cell membrane as observed using scanning electron microscopy (SEM). The chalcone derivatives thus synthesized could become potential alternative templates for novel antiviral and antibacterial agents.

Biological activity evaluation and action mechanism of chalcone derivatives containing thiophene sulfonate.

A series of novel chalcone derivatives containing a thiophene sulfonate group were designed and synthesized. The structures of all title compounds were determined by 1H-NMR, 13C-NMR and HRMS. Antibacterial bioassays indicated that, compound 2l demonstrated excellent antibacterial activities against Xanthomonas axonopodis pv. citri (Xac), with an EC50 value of 11.4 µg mL-1, which is significantly superior to those of bismerthiazol (BT) (51.6 µg mL-1) and thiodiazole-copper (TC) (94.7 µg mL-1). Meanwhile, the mechanism of action of compound 2l was confirmed by using scanning electron microscopy (SEM). In addition, compound 2e showed remarkable inactivation activity against Tobacco mosaic virus (TMV), with an EC50 value of 44.3 µg mL-1, which was superior to that of ningnanmycin (120.6 µg mL-1). Microscale thermophoresis (MST) also showed that the binding of compounds 2e and 2h to Tobacco mosaic virus coat protein (TMV-CP) yielded K d values of 0.270 and 0.301 µmol L-1, which are better than that of ningnanmycin (0.596 µmol L-1). At the same time, molecular docking studies for 2e and 2h with TMV-CP (PDB code: 1EI7) showed that the compound was embedded well in the pocket between the two subunits of TMV-CP in each case. These results suggested that chalcone derivatives containing a thiophene sulfonate group may be considered as activators in the design of antibacterial and antiviral agents.

Design, Synthesis, and Biological Activity of Novel Myricetin Derivatives Containing Amide, Thioether, and 1,3,4-Thiadiazole Moieties.

A series of myricetin derivatives containing amide, thioether, and 1,3,4-thiadiazole moieties were designed and synthesized, and their antiviral and antibacterial activities were assessed. The bioassays showed that all the title compounds exhibited potent in vitro antibacterial activities against Xanthomonas citri (Xac), Ralstonia solanacearum (Rs), and Xanthomonas oryzae pv. Oryzae (Xoo). In particular, the compounds 5a, 5f, 5g, 5h, 5i, and 5l, with EC50 values of 11.5⁻27.3 µg/mL, showed potent antibacterial activity against Xac that was better than the commercial bactericides Bismerthiazol (34.7 µg/mL) and Thiodiazole copper (41.1% µg/mL). Moreover, the in vivo antiviral activities against tobacco mosaic virus (TMV) of the target compounds were also tested. Among these compounds, the curative, protection, and inactivation activities of 5g were 49.9, 52.9, and 73.3%, respectively, which were better than that of the commercial antiviral Ribavirin (40.6, 51.1, and 71.1%, respectively). This study demonstrates that myricetin derivatives bearing amide, thioether, and 1,3,4-thiadiazole moieties can serve as potential alternative templates for the development of novel, highly efficient inhibitors against plant pathogenic bacteria and viruses.