Allicin-Inspired Heterocyclic Disulfides as Novel Antimicrobial Agents

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 S8 demonstrated the most potent antifungal activity in vitro against Monilinia fructicola (M. fructicola), with an EC50 value of 5.92 mu g/mL. Furthermore, an in vivo bioassay revealed that compound S8 exhibited equivalent curative and higher protective effects as the positive drug thiophanate methyl at a concentration of 200 mu g/mL. The preliminary mechanism experiments showed that compound S8 could inhibit the growth of M. fructicola' s hyphae in a time-and concentration-dependent manner, and compound S8 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 S5 also demonstrated an excellent antibacterial effect on Xanthomonas oryzae (X. oryzae), with a MIC90 value of 1.56 mu g/mL, which was superior to the positive control, thiodiazole copper.

Automated summary

In this study, a series of derivatives containing different functional groups were designed and synthesized based on the biological activities of allicin disulfide bond. Compound S8 exhibited potent antifungal activity against Monilinia fructicola in vitro and demonstrated therapeutic and protective effects in vivo. Furthermore, compound S5 showed excellent antibacterial effect on Xanthomonas oryzae.