Allicin-Inspired Heterocyclic Disulfides as Novel Antimicrobial Agents

Abstract

In this work, a series of derivatives with disulfide bonds containing pyridine, pyrimidine, thiophene, thiazole, benzothiazole, and quinoline were designed and synthesized based on the various biological activities of allicin disulfide bond functional groups. The antimicrobial activities of the target compounds were determined, and the structure-activity relationships were discussed. Among them, compound <b>S8</b> demonstrated the most potent antifungal activity in vitro against <i>Monilinia fructicola</i> (<i>M. fructicola</i>), with an EC₅₀ value of 5.92 μg/mL. Furthermore, an in vivo bioassay revealed that compound <b>S8</b> exhibited equivalent curative and higher protective effects as the positive drug thiophanate methyl at a concentration of 200 μg/mL. The preliminary mechanism experiments showed that compound <b>S8</b> could inhibit the growth of <i>M. fructicola</i>' s hyphae in a time- and concentration-dependent manner, and compound <b>S8</b> could induce the shrinkage of hyphae, disrupt the integrity of the plasma membrane, and cause the damage and leakage of cell contents. More than that, compound <b>S5</b> also demonstrated an excellent antibacterial effect on <i>Xanthomonas oryzae</i> (<i>X. oryzae</i>), with a MIC₉₀ value of 1.56 μg/mL, which was superior to the positive control, thiodiazole copper.