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

Abstract

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 <i>Xanthomonas citri</i> (<i>Xac</i>), <i>Ralstonia solanacearum</i> (<i>Rs</i>), and <i>Xanthomonas oryzae pv. Oryzae</i> (<i>Xoo</i>). In particular, the compounds <b>5a</b>, <b>5f</b>, <b>5g</b>, <b>5h</b>, <b>5i,</b> and <b>5l</b>, with EC₅₀ values of 11.5⁻27.3 μg/mL, showed potent antibacterial activity against <i>Xac</i> 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 <b>5g</b> 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.